Dr Iwan tem Cell Therapy Information Center (continiu)

Regrow or Repair: Potential Regenerative Therapies for the Kidney

 

Even if an adult stem cell population does exist in the adult kidney, would it remain in an end-stage kidney?

 

Indeed, the adoption of any organ-based cellular therapy is likely to succeed only if chronic renal disease can be diagnosed early and if such therapies are implemented well before end-stage renal failure is reached.

 

As we move closer to that point in time, the ethical debate about whether trials can proceed before ESRD will become critical.

 

 A lack of surrogate end points with which to assess the success of a cellular therapy in renal disease will make clinical trails long and expensive, eroding the will of the developers to continue to support the trials.

 

Read the studies report below

 

  1. 1.       Melissa H. Little

+Author Affiliations

  1. Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland, Australia
  2. Address correspondence to:
    Prof. Melissa H. Little, Institute for Molecular Bioscience, Queensland Bioscience Precinct, University of Queensland, St. Lucia, Brisbane, Qld, 4072, Australia. Phone: +61-7-3346-2054; Fax: +61-7-3346-2101;m.little@imb.uq.edu.au; Web: www.imb.uq.edu.au

Next Section

 

Abstract

Regenerative medicine is being heralded in a similar way as gene therapy was some 15 yr ago. It is an area of intense excitement and potential, as well as myth and disinformation. However, with the increasing rate of end-stage renal failure and limited alternatives for its treatment, we must begin to investigate seriously potential regenerative approaches for the kidney. This review defines which regenerative options there might be for renal disease, summarizes the progress that has been made to date, and investigates some of the unique obstacles to such treatments that the kidney presents. The options discussed include in situ organ repair via bone marrow recruitment or dedifferentiation;ex vivo stem cell therapies, including both autologous and nonautologous options; and bioengineering approaches for the creation of a replacement organ.

 the complete info exist please contact

Regenerative Approaches to Renal Disease

The term regenerative medicine straddles cell biology, matrix biology, and bioengineering with the objective to regrow or repair a damaged organ or tissue type. It can be defined as the use of cells for the treatment of disease and encompasses both organ repair and the de novo regeneration of an entire organ

Organ repair can be delivered in situ or ex vivo.

 

The simplest and most pharmacologically attractive strategy for organ repair in situ is the delivery of a soluble reparative factor that improves the ability of the kidney to repair itself.

 

Although such an approach may involve the understanding of the factors that are produced by stem cells, this is not a cellular therapy and is not dealt with in this review.

Other in situ possibilities include the recruitment of stem cells to the kidney to elicit repair and the induction of dedifferentiation of resident renal cells.

 

Whereas some regard in situ approaches as more likely to be successful for an architecturally and anatomically constrained organ such as the kidney, the other approach is the ex vivo culture of stem cells for redelivery to the damaged kidney.

 

This might involve autologous or nonautologous stem cells from a variety of sources. Finally, a bioengineering approach that relies on cells, factors, and matrix may be achievable. Although seemingly the most difficult, it may be the more feasible approach for genetic conditions such as polycystic kidney disease

This review investigates each option and relates it to the function and the structure of the kidney so as to examine its feasibility and identify the key obstacles to delivery.

Setting the Stage: Normal Kidney Development and Regeneration in Vertebrates

Regenerative biology draws on an understanding of normal developmental processes.

Understanding the molecular basis of kidney development will be the key to the development of regenerative therapies for chronic renal disease.

 

During mammalian development, three separate excretory organs develop: The pronephros, the mesonephros, and the metanephros.

 

 In mammals, it is the paired metanephroi that persist postnatally and constitute the permanent kidney.

 

 

 

The permanent kidney arises via reciprocal interactions between two tissues, the ureteric bud (UB) and the metanephric mesenchyme (MM), the latter arising from the intermediate mesoderm (IM) (1).

 

The UB gives rise to the collecting ducts and the ureter.

 

The MM, which shows much broader potential and gives rise to all other elements of the nephrons, the interstitium, and the vasculature, is regarded as the renal progenitor population (2).

 

 As the UB reaches the MM, signals from the tips of the branching UB induce areas of adjacent MM to aggregate and undergo a mesenchyme-to-epithelial (MET) transition.

 

Each MET event represents the birth of a new nephron with the first nephrons “born” in the center of the MM.

 

The peripheral MM, which has not yet undergone induction, is referred to as the nephrogenic zone.

 

Nephrogenesis in humans is complete by week 36 of gestation (3), whereas it continues for 1 to 2 wk after birth in the mouse and the rat. At that time, it is assumed that the peripheral nephrogenic zone is exhausted.

 

 

 

 

Can the kidney regenerate?

 In simple vertebrates, including fish and amphibians, metanephroi do not form and the permanent excretory unit is the mesonephros. Elasmobranchs (sharks, rays, and skates) constitute a unique example of “kidney” regeneration;

 

their mesonephroi can undergo accelerated nephrogenesis after partial ablation to replace the missing parts (4).

 

In the mammal, partial nephrectomy stimulates hypertrophy of remaining tissue, even in the contralateral kidney, but not the generation of new nephrons (5).

 

However, whereas the resection of an adult kidney does not lead to the regeneration achieved in the liver, the mammalian kidney shares with the majority of organs the ability to repopulate and repair structures that have sustained some degree of injury.

 

This process, termed cellular repair, can be achieved by reentry into mitosis and proliferation of neighboring cells.

 

 

 

 

 

As a result, the kidney can undergo significant remodeling in response to acute damage.

 

For example, obstruction of the ureter can result in the near destruction of the kidney medulla, but once the obstruction is removed, there is a rapid process of reconstruction and repair that will regenerate the tubules of the medulla without forming new nephrons (6).

 

It has been proposed that the cells that elicit such repair come from interstitial cell transdifferentiation (7),

 

 tubular cell dedifferentiation and migration into the areas of damage before redifferentiation (8,9),

 

the recruitment of stem cells from the bone marrow (1014), or the generation of new tubular cells from an endogenous renal stem cell population (reviewed in reference [15]).

 

Which of these is primarily responsible for the cellular repair that is observed after acute damage has not been proved definitively using lineage tracing.

 

However, the mammalian kidney seems to have a very limited potential for structural repairor true regeneration.

 

 

 

While nephrogenesis is occurring in the fetus, there is evidence that a systemic humoral response to nephrectomy allows the enhanced nephrogenesis of the remaining organ (16).

 

 However, nephrogenesis in mammals ceases just before or shortly after birth (3), and the birth of new nephrons has never been reported after this point in time.

 

Chronic injury of the kidney, which is responsible for the majority of cases of end-stage renal failure, results in irreversible glomerular and tubular damage and resultant loss of renal function.

Hence, mammalian kidneys respond to chronic damage by fibrosis, scarring, and irreversible functional loss

Recruitment of Bone Marrow to the Kidney

Can we improve the capacity of the kidney for cellular repair?

 

 The ability of cells that originate from bone marrow to move into distant sites within the body, including the kidney, is now well recognized.

 

 

 

 

 

 

 

 

 

 

 

 Reports have suggested that

 

these cells can transdifferentiate into tubular epithelial cells (12), mesangial cells (11,13,14), glomerular endothelial cells (17,18), and even podocytes (12).

 

 As in most organs, bone marrow–derived cells (BMDC) appear in the kidney in response to damage.

 

The lineage of these cells is unclear, and their ability to elicit transdifferentiation is controversial because the possibility of cell fusion has not always been eliminated (19) (Figure 2).

 

 

 

 

 

The use of lineage tracing has been critical to differentiating these two possibilities. In the case of the muscle, there is evidence from studies in which bone marrow was derived from LysM-Cre mice that it is the monocytic lineage that is recruited and fuses with cells in the target organ (20).

 

This lineage gives rise to the macrophages, which express proteins that are involved in fusion processes.

 

 This does not answer the question of the relative value of this fusion process.

 

 In the brain, BMDC can fuse with Purkinje cells (21), a cell type that is presumed to be unable to divide, possibly leading to a “rejuvenation” of such terminally differentiated cell types. Certainly, the functional outcome of BMDC recruitment must always be assessed.

 

In the context of the kidney, several studies have examined the recruitment of BMDC to kidney in response to damage signals and their transdifferentiative and reparative capacity. The injury models used include ischemia-reperfusion injury (22), folic acid–induced acute tubular injury (23,24), unilateral ureteric obstruction (25), and anti-Thy1 antibody–mediated glomerulonephritis (13).

 

 

 Bone marrow transplantation into HIgA mice, which have glomerulonephritis, improved renal function in these mice (26).

 

 In the studies in which careful quantification of recruitment to the tubular epithelium has been performed, donor-derived bone marrow has contributed between 0.06 and 11% of the epithelial cells (2224).

 

This level does decline with time. An initial recruitment level of 11% dropped to 0.67% at 28 d after ischemia with a concomitant increase in recruitment to the interstitium (22).

 

Two seminal papers in this area (22,23) disagreed on whether there was evidence for transdifferentiation, but both concluded that while BMDC recruitment occurs, repair is predominantly elicited via proliferation of endogenous renal cells. Duffield et al. (23) maintain that BDMC contribute a regenerative cytokine environment that may be important in the resulting functional repair

If this process could be recapitulated pharmacologically, then repair may occur without the need for recruitment.

 

 

 

 

 

Pretreatment of animals with stem cell factor and granulocyte colony-stimulating factor (granulocyte CSF) has been shown to improve recovery from ischemic injury in the absence of transdifferentiation of BMDC (27), and the combined pretreatment with granulocyte CSF and macrophage CSF provides renoprotection from cisplatin-induced renal failure (28). It also may prove valuable to improve recruitment. Held et al. (29) used a genetically induced model of chronic tubular damage that involved hereditary tyrosinemia (mutations in fumarylacetoacetate hydrolase) and mutations in homogentisic acid dioxygenase and reported significant integration (50%) of introduced BMDC.

 

 Hence, a drive for the selection of wild-type cells considerably increases the regeneration process (29). More recently, recruitment and apparent podocytic transdifferentiation of male BMDC to the glomeruli of mice that lacked collagen4α3 has been reported (30).

 

This is a model of Alport syndrome in which there is considerable shedding of protein through the damaged glomerular basement membrane.

 

Whereas podocytes have not been a reported site of bone marrow recruitment in other experimental models,

 

 this study claimed a bone marrow origin for 10% of the podocytes in these mice with a reduction in protein shedding and evidence of collagen replacement within the basement membrane.

 

In this case, access may have been increased as a result of the altered permeability of the basement membrane, but BMDC from mutant mice were not recruited to the glomeruli of mutant recipients, suggesting an active selection for collagen-producing cells.

 

 

 In all of these reports of bone marrow recruitment to damaged kidneys, the lineage of the BMDC that were recruited has not been established. However, adoptive transfer of macrophages into a model of unilateral ureteric obstruction significantly reduced fibrosis in the late stages of this damage state (25).

 

This may have involved transdifferentiation or an altered immunologic response. What also has not been investigated is whether the recruitment of BMDC is good or bad in cases of chronic renal damage

Controlled Dedifferentiation as a Treatment of Renal Disease

Can we repair a kidney by recapitulating development?

Among vertebrates, certain amphibians show a unique ability to regenerate completely complex organs or body parts (31).

 

Salamanders, newts, and axolotls can reconstitute various anatomic structures such as limbs, spinal cord, heart, tail, retina, lens, and upper and lower jaws. In the case of the limb, this process involves dedifferentiation (i.e., loss of a specialized phenotype to return to a progenitor phenotype), proliferation of the resulting primitive blastema, and then redifferentiation of cells in the vicinity of the injury (32) as opposed to the mobilization of a stem cell population per se.

 

Muscle fibers, Schwann cells, periosteal cells, and cells from the connective tissue undergo dedifferentiation and then organize a blastema from which the new limb arises (Figure 3A). Can this be applied in higher vertebrates?

 

Regeneration within the skate mesonephros is a process that takes place in an identified nephrogenic zone using a persistent field of progenitors that can be recruited for regeneration (Figure 3B).

 

Whether these progenitors represent stem cells, as defined as a long-term, self-renewing cell population, has not been established. In mammals, there is no persistent blastema in the adult (Figure 3C).

 

In the absence of such a persistent population of renal progenitors, could such a blastemal field be generated via dedifferentiation in the mammalian kidney?

 

In a recent review of the obstacles to limb regeneration in the mammal (33), it was observed that mammalian limb cells lack the response of reentry into S-phase in response to thrombin (even though this response still would be present if a mouse cell were fused with that of a salamander), and their more complex immune systems respond to damage via the production of fibrosis and the recruitment of inflammatory cells.

 

Possibly as a result of these differences, the production of the blastema that is required for regeneration does not occur, yet there are examples of cell types even in humans that show enormous regenerative capacities, together with more salamander-like properties such as an ability to recommence cell division and dedifferentiate to regenerate.

 

 

 

 

 

 

 

Oligodendrocyte precursor cells have been reverted to multipotential neural stem cells that are able to proliferate and to give rise to neurons, astrocytes, and oligodendrocytes (34).

 

More striking, highly specialized multinucleated muscle cells have been induced to dedifferentiate into mononucleated multipotent progenitor cells that are able to adopt the osteogenic, chondrogenic, adipogenic, and myogenic fates (35).

 

In this case, the dedifferentiation was induced by ectopic expression of the transcriptional repressor Msx1 in combination with growth factor stimulation.

 

Finally, the mouse MRL strain has been shown to have both a marked capacity not to scar and to restore normal myocardial tissue without scarring through a process the authors describe as similar to regeneration in amphibians (36).

 

How feasible is dedifferentiation as a therapy?

 

Postnatal cell turnover in the kidney has never been examined thoroughly, but the cellular complexity of this organ suggests that a dedifferentiation into blastema followed by redifferentiation for the purposes of regeneration would need to be as complex as that seen in the salamander limb.

 

 Hence, we need to understand the blastemal progenitors that give rise to the kidney and to understand the process that long has been observed in the kidney in response to short-term local damage:

 

 

 

 The epithelial-to-mesenchymal transition of tubular cells.

 

If able to be induced, then dedifferentiation might be evoked in situ or ex vivo (Figure 4). In situdedifferentiation would require controllable gene therapy to ensure a cessation of dedifferentiation and subsequent induction of regeneration, or it runs the risk of generating blastemal expansions as for a Wilms’ tumor.

 

 

 

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Dr Iwan Stem cell Therapy Information Center (continiu)

FOUNDER
 
Dr Iwan Suwandy,MHA
 
more info contact
 
iwansuwandy@ gmail.com
 
all free of charge
 
this info to all human in the world
with
 
THE MIGHTY GOD BLESS
 
 
PHYSIOLOGY  and  PATOPHISIOLOGY OF THE STEM CELL
 
 
 

STEM CELL PHYSIOLOGY

There are many cell of blood and immune body are continuously produced throughout life from hemopoietic stem cells residing in the bone marrow.

The ability of these cells to perform this function is why bone-marrow transplants can be used to treat leukemia and other blood or immune disorders.

Researchers in the Stem Cell Physiology Research Unit, located at The Biomedical Research Centre at UBC, are studying the biology of bone marrow stem cells and the immune system.

They are focusing on understanding the molecular mechanisms that control how bone-marrow stem cells self-renew and how they differentiate into and function as specific types of blood cells.

Their long-term goal is to understand how defence, repair, and regeneration are regulated and how this knowledge can be exploited to benefit health and offer new treatments for disease.

The Biomedical Research Centre’s researchers recently made important discoveries about the ways bone marrow stem cells differentiate into various types of cells that can fuse with cells in other tissues – such as brain or muscle – to contribute genes.

EAD MORE INFO

ABOUT BONE MARROW  STEM CELL

Mesenchymal stem cells: the ‘other’ bone marrow stem cells

Last updated: 

20 Jun 2012

Mesenchymal stem cells: the 'other' bone marrow stem cells

Mesenchymal stem cells (MSCs) can make several types of cells belonging to our skeletal tissues, such as cartilage, bone and fat. Scientists are investigating how MSCs might be used to treat bone and cartilage diseases. Some MSC research is also exploring therapies for other diseases, but the scientific basis for these applications has not yet been established or widely accepted.

Did you know?

Mesenchymal stem cells make up about 0.001-0.01% of all the cells in your bone marrow

Human mesenchymal stem cells grown in a single layer on the bottom of a flask; 4x magnificationHuman mesenchymal stem cells grown in a single layer on the bottom of a flask; 4x magnification 

Human mesenchymal stem cells grown in a single layer on the bottom of a flask; 10x magnificationHuman mesenchymal stem cells grown in a single layer on the bottom of a flask; 10x magnification 

Bone cells made from MSCs; the colour is from a stain used to mark the bone cells (von Kossa stain) Bone cells made from MSCs; the colour is from a stain used to mark the bone cells (von Kossa stain) 

Fat cells made from MSCs; the colour is from a stain called Nile red O that marks fat cells red Fat cells made from MSCs; the colour is from a stain called Nile red O that marks fat cells red 

Cartilage cells made from MSCs; cartilage cells are stained red using the dye Safranin O Cartilage cells made from MSCs; cartilage cells are stained red using the dye Safranin O 

Cartilage cells made from MSCs; the cartilage cells are marked brown by a process called immunostainingCartilage cells made from MSCs; the cartilage cells are marked brown by a process called immunostaining 

What can mesenchymal stem cells do?

Mesenchymal stem cells (MSCs) are an example of tissue or ‘adult’ stem cells. They are ‘multipotent’, meaning they can produce more than one type of specialized cell of the body, but not all types. MSCs make the different specialized cells found in the skeletal tissues. For example, they can differentiate − or specialize  −  into cartilage cells (chondrocytes), bone cells (osteoblasts) and fat cells (adipocytes). These specialized cells each have their own characteristic shapes, structures and functions, and each belongs in a particular tissue.

Some early research suggested that MSCs might also differentiate into many different types of cells that do not belong to the skeletal tissues, such as nerve cells, heart muscle cells, liver cells and endothelial cells, which form the inner layer of blood vessels. These results have not been confirmed to date. In some cases, it appears that the MSCs fused together with existing specialized cells, leading to false conclusions about the ability of MSCs to produce certain cell types. In other cases, the results were an artificial effect caused by chemicals used to grow the cells in the lab.

Mesenchymal stem cell differentiation: MSCs can make fat, cartilage and bone cells. They have not been proven to make other types of cells of the body.

Mesenchymal stem cell differentiation: MSCs can make fat, cartilage and bone cells. They have not been proven to make other types of cells of the body.

Where are mesenchymal stem cells found?

MSCs were originally found in the bone marrow. There have since been many claims that they also exist in a wide variety of other tissues, such as umbilical cord blood, adipose (fat) tissue and muscle. It has not yet been established whether the cells taken from these other tissues are really the same as, or similar to, the mesenchymal stem cells of the bone marrow.

The bone marrow contains many different types of cells. Among them are blood stem cells (also called hematopoietic stem cells; HSCs) and a variety of different types of cells belonging to a group called ‘mesenchymal’ cells. Only about 0.001-0.01% of the cells in the bone marrow are mesenchymal stem cells.

It is fairly easy to obtain a mixture of different mesenchymal cell types from adult bone marrow for research. But isolating the tiny fraction of cells that are mesenchymal stem cells is more complicated. Some of the cells in the mixture may be able to form bone or fat tissues, for example, but still do not have all the properties of mesenchymal stem cells. The challenge is to identify and pick out the cells that can both self-renew (produce more of themselves) and can differentiate into three cell types – bone, cartilage and fat. Scientists have not yet reached a consensus about the best way to do this.

Developing new treatments using mesenchymal stem cells

No treatments using MSCs are yet available. However, several possibilities for their use in the clinic are currently being explored.

AFTER STUDY THE PHYSIOLOGY,HISTOLOGY AND PATOPHYSIOLOGY OF CELL

AND STEM CELL, I HAVE MADE CONCLUSION THE ONLY WAYTO REPAIR THE

DIABETIC NEPHRPTAHY ARE

THE STEM CELL THERAPY

LET’S WE STUDYTHE THE DIABETIC NEPHROPATHY STEM CELL THERAPY AROUND THE WORLD

 

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Driwan Stem Cell Therapy Infprmation Center(continiu)

FOUNDER
 
Dr Iwan Suwandy,MHA
 
more info contact
 
iwansuwandy@ gmail.com
 
all free of charge
 
this info to all human in the world
with
 
THE MIGHTY GOD BLESS
 
 
PHYSIOLOGY  and  PATOPHISIOLOGY OF THE STEM CELL
 
 
 

STEM CELL PHYSIOLOGY

There are many cell of blood and immune body are continuously produced throughout life from hemopoietic stem cells residing in the bone marrow.

The ability of these cells to perform this function is why bone-marrow transplants can be used to treat leukemia and other blood or immune disorders.

Researchers in the Stem Cell Physiology Research Unit, located at The Biomedical Research Centre at UBC, are studying the biology of bone marrow stem cells and the immune system.

They are focusing on understanding the molecular mechanisms that control how bone-marrow stem cells self-renew and how they differentiate into and function as specific types of blood cells.

Their long-term goal is to understand how defence, repair, and regeneration are regulated and how this knowledge can be exploited to benefit health and offer new treatments for disease.

The Biomedical Research Centre’s researchers recently made important discoveries about the ways bone marrow stem cells differentiate into various types of cells that can fuse with cells in other tissues – such as brain or muscle – to contribute genes.

EAD MORE INFO

ABOUT BONE MARROW  STEM CELL

Mesenchymal stem cells: the ‘other’ bone marrow stem cells

Last updated: 

20 Jun 2012

Mesenchymal stem cells: the 'other' bone marrow stem cells

Mesenchymal stem cells (MSCs) can make several types of cells belonging to our skeletal tissues, such as cartilage, bone and fat. Scientists are investigating how MSCs might be used to treat bone and cartilage diseases. Some MSC research is also exploring therapies for other diseases, but the scientific basis for these applications has not yet been established or widely accepted.

Did you know?

Mesenchymal stem cells make up about 0.001-0.01% of all the cells in your bone marrow

Human mesenchymal stem cells grown in a single layer on the bottom of a flask; 4x magnificationHuman mesenchymal stem cells grown in a single layer on the bottom of a flask; 4x magnification

Human mesenchymal stem cells grown in a single layer on the bottom of a flask; 10x magnificationHuman mesenchymal stem cells grown in a single layer on the bottom of a flask; 10x magnification

Bone cells made from MSCs; the colour is from a stain used to mark the bone cells (von Kossa stain) Bone cells made from MSCs; the colour is from a stain used to mark the bone cells (von Kossa stain)

Fat cells made from MSCs; the colour is from a stain called Nile red O that marks fat cells red Fat cells made from MSCs; the colour is from a stain called Nile red O that marks fat cells red

Cartilage cells made from MSCs; cartilage cells are stained red using the dye Safranin O Cartilage cells made from MSCs; cartilage cells are stained red using the dye Safranin O

Cartilage cells made from MSCs; the cartilage cells are marked brown by a process called immunostainingCartilage cells made from MSCs; the cartilage cells are marked brown by a process called immunostaining

What can mesenchymal stem cells do?

Mesenchymal stem cells (MSCs) are an example of tissue or ‘adult’ stem cells. They are ‘multipotent’, meaning they can produce more than one type of specialized cell of the body, but not all types. MSCs make the different specialized cells found in the skeletal tissues. For example, they can differentiate − or specialize  −  into cartilage cells (chondrocytes), bone cells (osteoblasts) and fat cells (adipocytes). These specialized cells each have their own characteristic shapes, structures and functions, and each belongs in a particular tissue.

Some early research suggested that MSCs might also differentiate into many different types of cells that do not belong to the skeletal tissues, such as nerve cells, heart muscle cells, liver cells and endothelial cells, which form the inner layer of blood vessels. These results have not been confirmed to date. In some cases, it appears that the MSCs fused together with existing specialized cells, leading to false conclusions about the ability of MSCs to produce certain cell types. In other cases, the results were an artificial effect caused by chemicals used to grow the cells in the lab.

Mesenchymal stem cell differentiation: MSCs can make fat, cartilage and bone cells. They have not been proven to make other types of cells of the body.

Mesenchymal stem cell differentiation: MSCs can make fat, cartilage and bone cells. They have not been proven to make other types of cells of the body.

Where are mesenchymal stem cells found?

MSCs were originally found in the bone marrow. There have since been many claims that they also exist in a wide variety of other tissues, such as umbilical cord blood, adipose (fat) tissue and muscle. It has not yet been established whether the cells taken from these other tissues are really the same as, or similar to, the mesenchymal stem cells of the bone marrow.

The bone marrow contains many different types of cells. Among them are blood stem cells (also called hematopoietic stem cells; HSCs) and a variety of different types of cells belonging to a group called ‘mesenchymal’ cells. Only about 0.001-0.01% of the cells in the bone marrow are mesenchymal stem cells.

It is fairly easy to obtain a mixture of different mesenchymal cell types from adult bone marrow for research. But isolating the tiny fraction of cells that are mesenchymal stem cells is more complicated. Some of the cells in the mixture may be able to form bone or fat tissues, for example, but still do not have all the properties of mesenchymal stem cells. The challenge is to identify and pick out the cells that can both self-renew (produce more of themselves) and can differentiate into three cell types – bone, cartilage and fat. Scientists have not yet reached a consensus about the best way to do this.

Developing new treatments using mesenchymal stem cells

No treatments using MSCs are yet available. However, several possibilities for their use in the clinic are currently being explored.

Bone and cartilage repair
The ability of MSCs to differentiate into bone cells called osteoblasts has led to their use in early clinical trials investigating the safety of potential bone repair methods. These studies are looking at possible treatments for localized skeletal defects (damage at a particular place in the bone).

Other research is focussed on using MSCs to repair cartilage. Cartilage covers the ends of bones and allows one bone to slide over another at the joints. It can be damaged by a sudden injury like a fall, or over a long period by a condition like osteoarthritis, a very painful disease of the joints. Cartilage does not repair itself well after damage. The best treatment available for severe cartilage damage is surgery to replace the damaged joint with an artificial one. Because MSCs can differentiate into cartilage cells called chondrocytes, scientists hope MSCs could be injected into patients to repair and maintain the cartilage in their joints. Researchers are also investigating the possibility that transplanted MSCs may release substances that will tell the patient’s own cells to repair the damage.

Many hurdles remain before this kind of treatment can become a reality. For example, when MSCs are transplanted, most of them are rapidly removed from the body. Researchers are working on new techniques for transplanting the cells, such as developing three-dimensional structures or scaffolds that mimic the conditions in the part of the body where the cells are needed. These scaffolds will hold the cells and encourage them to differentiate into the desired cell type.

Heart and blood vessel repair
Some studies in mice suggest that MSCs can promote formation of new blood vessels in a process called neovascularisation. MSCs do not make new blood vessel cells themselves, but they may help with neovascularisation in a number of ways. For example, they may release proteins that stimulate the growth of other cells called endothelial precursors – cells that will develop to form the inner layer of blood vessels. Such studies on animals have led researchers to hope that MSCs may provide a way to repair the blood vessel damage linked to heart attacks or diseases such as critical limb ischaemia. A number of early stage clinical trials using MSCs in patients are currently underway but it is not yet clear whether the treatments will be effective.

Inflammatory and autoimmune diseases
Several claims have been made that MSCs are able to avoid detection by the immune system and can be transplanted from one patient to another without risk of immune rejection by the body. However, these claims have not been confirmed by other studies. It has also been suggested that MSCs may be able to slow down the multiplication of immune cells in the body to reduce inflammation and help treat transplant rejection or autoimmune diseases. Again, this has yet to be proven and much more evidence is needed to establish whether MSCs could really be used for this kind of application.

Current research and the future

Research into therapies using MSCs is still in its infancy. A great deal more work is needed before such therapies can be used routinely in patients. Questions remain about how the cells can be controlled, how they will behave when transplanted into the body, how they can be delivered to the right place so that they work effectively and so forth. By studying how these cells work and interact within the body, researchers hope to develop safe and effective new treatments in the future..

source

Primary Investigator: 
 
 

Stem Cell Physiology and Pathophysiology

 Diabetes  and Hemopoetic Stem Cell
 
Why Diates impairs the interactions between long-term hematopoietic stem cells ?
to answer this question pleae read carefulyy the abstrct of this reseach

Diabetes impairs the interactions between long-term hematopoietic stem cells and osteopontin-positive cells in the endosteal niche of mouse bone marrow.

Abstract

Hematopoietic stem cells (HSCs) are maintained, and their division/proliferation and quiescence are regulated in the microenvironments, niches, in the bone marrow.

Although diabetes is known to induce abnormalities in HSC mobilization and proliferation through chemokine and chemokine receptors, little is known about the interaction between long-term

HSCs (LT-HSCs)

and

osteopontin-positive (OPN) cells

in

endosteal niche.

To examine this interaction, LT-HSCs and OPN cells were isolated from streptozotocin-induced diabetic and nondiabetic mice.

In diabetic mice, we observed a reduction in the number of LT-HSCs and OPN cells and impaired expression of Tie2, β-catenin, and N-cadherin on LT-HSCs and β1-integrin, β-catenin, angiopoietin-1, and CXCL12 on OPN cells.

In an in vitro coculture system,

LT-HSCs isolated from nondiabetic mice exposed to diabetic OPN cells showed abnormal mRNA expression levels of Tie2 and N-cadherin. Conversely,

in LT-HSCs derived from diabetic mice exposed to nondiabetic OPN cells, the decreased mRNA expressions of Tie2, β-catenin, and N-cadherin were restored to normal levels.

The effects of diabetic or nondiabetic OPN cells on LT-HSCs shown in this coculture system were confirmed by the coinjection of LT-HSCs and OPN cells into bone marrow of irradiated nondiabetic mice.

Our results

provide new insight into

the treatment of

diabetes-induced LT-HSC abnormalities

and suggest that

the replacement of OPN cells may represent a novel treatment strategy.

to understan this situation we must understand

the physiology of normal cell

Overview

  • The typical cell comprises a nucleus and cytoplasm, separated by the nuclear membrane
  • The cytoplasm is separated from interstitial fluid by the cell membrane
  • The different substances making up a cell are termed its “protoplasm” and include:
    • water (usually 70%-85%)
    • electrolytes – chiefly potassium, magnesium, phosphate, sulphate, bicarbonate, and a little sodium, chloride and calcium
    • proteins (usually 10%-20%) – structural and globular, including enzymes
    • lipids (usually 2%) – particularly phospholipids, cholesterol, triglycerides, neutral fats
    • carbohydrates (usually 1%) – usually as glycogen
  • The cell and its organelles are surround by membranes composed of lipids and proteins
    • these include the cell membrane, nuclear membrane, and membranes of the ER, mitochondria, lysosomes and Golgi apparatus
    • each prevents free movement of water and water-soluble substances between cell compartments
  • The cell membrane is a lipid bilayer with inserted proteins
    • the lipid bilayer is mostly phospholipids and cholesterol
    • it is permeable to lipid-soluble substances, but is a major barrier to water-soluble substances such as ions
    • integral proteins protrude through the membrane, while peripheral proteins are attached to the inner surface
    • many integral proteins form structural channels, or carrier proteins
    • peripheral proteins are usually enzymes
    • the membrane is studded with glycoproteins, which are thought to repel other negatively charged molecules, allow attachment to some other cells and act as receptors for binding hormone
  • The ER synthesizes substances in the cell
    • aided by a large surface area
    • materials made include proteins, carbohydrates, lipids, lysosomes, peroxisomes, and secretory granules
    • lipids are made within the ER wall
    • proteins are made by mRNA attaching to ribosomes on the outer surface of the ER
  • The Golgi apparatus is prominent in secretory cells
    • synthesis of lysosomes, secretory vesicles and other cytoplasmic inclusions
    • transport vesicles are pinched-off bits of ER which then fuse with the Golgi apparatus
  • Lysosomes provide the cell with a digestive system
    • small round vesicles containing digestive enzymes
    • usually cordoned-off by a non-reactive membrane
  • Mitochondria release energy in the cell
    • via the citric acid cycle and oxidative enzymes, producing ATP
    • self-replicative and almost certainly originally symbiotic
  • The nucleus acts as a control centre of the cell and contains large amounts of DNA
    • separated from the cytoplasm by a nuclear envelope, pierced by several thousand pores
    • most also contain one or more nucleoli, which do not have membranes; these contain large amounts of RNA, and are enlarged in cells actively synthesizing proteins

Ingestion by the Cell – Endocytosis

  • Small particles enter the cell through diffusion or active transport. Very large particles enter by endocytosis, either pinocytosis or phagocytosis
  • Pinocytosis is the ingestion of small globules of extracellular fluid, forming minute vesicles in the cytoplasm
  • Phagocytosis is the ingestion of large particles such as bacteria, cells, and bits of degenerating tissue
  • Substances so absorbed are digested in the cell by lysosomes. The products of digestion are small amino acids, lipids, glucose, phosphate

Synthesis of Cellular Structures

  • The synthesis of most structures begins in the ER. The rough ER is so named because large numbers of ribosomes attach to the outer surface. Small ER vesicles continually break off from the smooth ER and migrate to the Golgi apparatus.

Extraction of Energy by Mitochondria

  • Almost all oxidative reactions occur inside mitochondria and the energy released is in the form of ATP. ATP has two very labile high-energy phosphate bonds (12,000 calories per mole)
  • Most of the ATP produced in cells is made by mitochondria. About 5% is made by glycolysis, the rest by the citric acid cycle. The process is called the “chemosmotic mechanism”
  • ATP is used for many cellular functions, particularly membrane transport (Na-K-ATPase), synthesis of chemical compounds, and mechanical work

Locomotion and Ciliary Movements by Cells

  • Amoeboid locomotion is the movement of an entire cell in relation to its surroundings (eg. a white blood cell through tissues). It begins with protrusion of a pseudopodium from one end of the cell, with continual exocytosis, and continual endocytosis of the membrane at the mid and rear portions of the cell.
  • Two effects are essential to forward movement: attachment of the pseudopodium, and adequate energy for the movement. In the cytoplasm are molecules of the protein actin, which polymerize to form a filamentous network that contracts on binding to another protein such as myosin.
  • Amoeboid movement is initiated usually by a chemotactic factor. The process is called chemotaxis.
  • Ciliary movement is a whip-like movement of cilia on the surface of cells (only in the respiratory tract, and in the uterine tubules). The mechanism is not known.

Genetic Control of Cell Function

  • Cell genes control protein synthesis. Each gene is a double-stranded helical molecule of DNA that controls the formation of RNA. RNA spreads through the cell to control the formation of a specific protein.
  • Nucleotides are organized to form two strands of DNA bound loosely to each other. There are three building blocks: phosphoric acid, deoxyribose (a sugar), and four nitrogenous bases (two purines: adenine and guanine; two pyrimidines, thymine and cytosine). Adenine always bonds with thymine, and guanine always bonds with cytosine.
  • The genetic code consists of triplets of bases. Each is called a code word. These determine the sequence of amino acids added to the protein.
  • DNA code is transferred to RNA code by the process of transcription. It occurs in the nucleus, where each DNA code word forms a complementary RNA triplet called a codon. The basic building blocks are almost the same except ribose replaces deoxyribose, and uracil replaces thymine.
  • The next step is the activation of the nucleotide, with the addition of two phosphate radicals derived from ATP. It makes available large amounts of energy to promote the reactions that add each new RNA nucleotide to the end of the RNA chain.
  • The DNA strand is used as a template to assemble the RNA molecule from activated nucleotides, under the influence of the enzyme RNA polymerase.
  • There are three different types of RNA:
    • mRNA, carries the genetic code to the cytoplasm to control the formation of proteins
    • rRNA, which along with proteins forms the ribosomes, the molecules in which proteins are actually assembled
    • tRNA, which transports activated amino acids to the ribosomes – 20 types for 20 amino acids
  • The operons of the DNA strand control biochemical synthesis and are activated by the promoter. The operon is controlled by a repressor and an activator operator, and through negative feedback by the cell product. I have no idea what this paragraph means.

The DNA Genetic System

  • With the exception of some very long-lived cells (eg. nerve cells), most cells need to be able to reproduce their own cell type.
  • Reproduction begins with replication of the DNA. As they are replicated, the DNA strands are repaired and proofread. Mistakes (mutations) rarely escape enzymes that cut out defective bits and replace them with appropriate complementary nucleotides.
  • Entire chromosomes (46, 23 pairs) are replicated. In addition to the DNA, there is a fair bit of protein as histones, molecules around which the DNA is coiled to pack it in. The two newly-formed chromosomes remain temporarily attached to each other at a point called the centromere, near the centre. The duplicated but still-attached chromosomes are called chromatids.

Mitosis

  • This is the process by which the cell splits into two new daughter cells.
  • Two pairs of centrioles, small structures close to one pole of the nucleus, begin to move apart. Microtubules grow radially away from each of the centriole pairs, forming a spiny star called the aster at each end of the cell. The complex of microtubules between the pairs is called the spindle, and the entire set of microtubules plus the pairs of centrioles the mitotic apparatus.
  • Prophase is the beginning of mitosis – while the spindle is forming, the chromosomes become condensed into defined chromosomes
  • Prometaphase is the stage at which microtubular spines puncture and fragment the nuclear envelope, and microtubules become attached to the chromatids at the centromere
  • Metaphase is the stage at which the two asters are pushed farther and farther apart
  • Anaphase is the stage at which the two chromatids of each chromosome are pulled apart at the centromere. All 46 pairs are separated, forming two sets of 46 daughter chromosomes.
  • Telophase is the stage at which the two sets of daughter chromosomes are pulled completely apart. Then the mitotic apparatus dissolves and a new nuclear membrane develops around each set of chromosomes.

MYELIN CELL

MYELIN AXON

Pada sel saraf

selubung Mielin 

Neuron-no labels.png

adalah lapisan fosfolipid 

yang membungkus akson secara konsentrik. 

MYELIN SHEATH

(SELUBUNG MYELIN)

Myelin Membrane Assembly Is Driven by a Phase Transition of Myelin Basic Proteins Into a Cohesive Protein Meshwork

  • Shweta Aggarwal,
     
  • Nicolas Snaidero,
     
  • Gesa Pähler,
     
  • Steffen Frey,
     
  • Paula Sánchez,
     
  • Markus Zweckstetter,
     
  • Andreas Janshoff,
     
  • Anja Schneider,
     
  • Marie-Theres Weil,
     
  • Iwan A. T. Schaap,
     
  • Dirk Görlich,
     
  • Mikael Simons

Abstract

Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system.

Author Summary

Myelin is a specialized membrane that covers axons and serves as an insulator to enable the fast conduction of the action potentials.

The importance of myelin membrane is highlighted in demyelinating diseases such as multiple sclerosis, which lead to severe neurological disability.

Here, we describe a physicochemical mechanism of how myelin is generated and assembled.

We find that myelin basic protein (MBP) molecules undergo a phase transition into a cohesive meshwork at the membrane interface, which drives structural changes in the membranes.

We provide evidence that the interaction of myelin basic proteins with the inner leaflet of the myelin bilayer results in charge neutralization and triggers self-association of the protein into larger polymers.

Interactions between MBP molecules are mediated by hydrophobic phenylalanine residues and amyloid-like association.

We propose that phase transition of MBP from a cytoplasmic soluble pool into a cohesive functional amyloid-like assembly is one of the key mechanisms in myelin membrane biogenesis

Sel Schwann

merupakan sel yang membentuk selubung

pada sistem saraf tepi,

sedangkan oligodendrosit merupakan sel yang membentuk selubung yang sama pada sistem saraf pusat.

Selubung mielin merupakan karakteristik dari vertebrata (gnathostome), tetapi juga diangkat oleh evolusi pararel beberapa invertebrata.[1] 

Mielin ditemukan oleh Louis-Antoine Ranvier pada tahun 1878.

SCHWAN CELL

LT-HSCs derived from diabetic


Cellular Injury and Adaptation

Overview

  • Tissue injury starts with molecular or structural damage to cells. When faced with injury, cells can either adapt, sustain reversible injury, or die. Cellular adaptation occurs when stressors result in a new but altered state that preserves viability of the cell (eg. hypertrophy, atrophy)
  • There are two morphologic patterns of cell death: apoptosis and necrosis
    • apoptosis is characterized by chromatin condensation and fragmentation, occurs singly or in small clusters only, and results in the elimination of unwanted cells during embryogenesis and some physiologic and pathologic states
    • necrosis is characterized by swelling, denaturation of proteins, breakdown of cellular organelles, and cell rupture

Causes of Cellular Injury

  • Hypoxia
    • ischaemia (loss of supply)
    • inadequate oxygenation (respiratory failure)
    • loss of oxygen-carrying capacity of the blood (anaemia, CO poisoning)
  • Physical agents
    • trauma
    • thermal insult
    • radiation
    • electric shock
  • Chemical agents and drugs
    • therapeutics
    • non-therapeutic agents
  • Infectious agents
    • viruses
    • rickettsiae
    • bacteria
    • fungi
    • parasites
  • Immunologic reactions
  • Genetic derangements
  • Nutritional imbalances

General Mechanisms of Cell Injury

  • Oxygen-derived free radicals are produced in many conditions and cause damage to cell structure and function
  • Loss of calcium homeostasis, with increased intracellular calcium – this activates phospholipases, proteases, ATPases and endonucleases
  • ATP depletion
  • Defects in membrane permeability

Ischaemic and Hypoxic Injury

  • The key is early loss of oxidative phosphorylation and ATP generation by mitochondria
  • Decreased ATP stimulates aerobic glycolysis; glycogen is quickly depleted and lactate and inorganic phosphate produced, dropping intracellular pH
  • Manifests histologically as swelling, from:
    • loss of Na-K-ATPase, causing sodium to enter the cell, potassium to leave, and an osmotic gain of water
    • increased intracellular osmotic load from the accumulation of lactate and inorganic phosphate
    • polarized membranes lose their polarity
  • All of these are reversible if oxygenation is restored
  • The sentinel event for irreversible injury seems to be damage to membranes
  • Calcium is probably the most important mediator of biochemical and morphologic alterations leading to cell death
  • Reperfusion injury
    • mechanism is not well understood, but clinically important particularly to myocardial and cerebral infarction
    • definition would be a loss of cells in addition to those irreversibly damaged, by restoration of oxygenation at the end of an ischaemic episode
    • bathing compromised cells in high concentrations of calcium when they can’t fully regulate their internal ionic environment?
    • local recruitment of inflammatory cells, releasing reactive species?
    • incomplete oxygen reduction by damaged mitochondria yielding reactive species?

Free Radical-Induced Injury

  • Free radicals are reactive, unstable species that interact with proteins, lipids and carbohydrates. They are created by absorption of radiant energy, oxidative metabolism, or enzymatic conversion of exogenous chemicals.
  • Important free radicals are superoxide (from oxygen), hydrogen peroxide, hydroxyls and nitric oxide.
  • They damage cells through peroxidation of lipids, cross-linking of proteins by forming disulfide bonds, inactivation of sulfhydryl enzymes, and induction of direct DNA damage
  • Free radical termination is by antioxidants (vitamin E, glutathione, ceruloplasmin, transferrin), or enzymes (superoxide dismutase, catalase, glutathione peroxidase)

Chemical Injury

  • Direct injury. Mercury is a good example, binding to sulfhydryl groups of cell membrane proteins, increasing permeability and inhibiting ATPase-dependent transport.
  • Indirect injury. Conversion to toxic metabolites (carbon tetrachloride).

 Abnormal cell injury in diabetic

Abnormal Cell Injury In Dibetes

Myelin splitting,

Schwann cell injury

and demyelination

in feline diabetic neuropathy

source

Abstract

Nerve biopsy samples from two cats with spontaneously occurring diabetes were examined.

The predominant nerve fiber abnormalities observed were restricted to the myelin sheath and Schwann cell.

Reactive, degenerative and proliferative Schwann cell changes were evident but the most striking abnormality encountered was splitting and ballooning of the myelin sheath.

These observations highlight

the significance of Schwann cell injury in the pathogenesis of diabetic neuropathy

THE PATHOGENESIS OF THE LATE COMPLICATIONS OF DIABETES MELLITUS.

Dr Angela Barbour. Discipline of Pathology

University of Adelaide

2009

This material has been reproduced and communicated to you by or on behalf of Adelaide University pursuant to Part

VB of the Copyright Act 1968 (the Act).

COMPLICATIONS OF DIABETES MELLITUS

 

Vascular

 

 

Large arteries (macroangiopathy): atherosclerosis and related complications

 

 

Arterioles: hyaline arteriolosclerosis

 

 

Microangiopathy/microvascular: capillary basement membrane thickening

 

 

Renal

 

 

Diabetic nephropathy

 

 

Osteoblasts and Bone Marrow Mesenchymal Stromal Cells Control Hematopoietic Stem Cell Migration and Proliferation in 3D In Vitro Model

  • Ana Paula D. N. de Barros,
     
  • Christina M. Takiya,
     
  • Luciana R. Garzoni,
     
  • Mona Lisa Leal-Ferreira,
     
  • Hélio S. Dutra,
     
  • Luciana B. Chiarini,
     
  • Maria Nazareth Meirelles,
     
  • Radovan Borojevic,
     
  • Maria Isabel D. Rossi

Abstract

Background

Migration, proliferation, and differentiation of hematopoietic stem cells (HSCs) are dependent upon a complex three-dimensional (3D) bone marrow microenvironment. Although osteoblasts control the HSC pool, the subendosteal niche is complex and its cellular composition and the role of each cell population in HSC fate have not been established. In vivo models are complex and involve subtle species-specific differences, while bidimensional cultures do not reflect the 3D tissue organization. The aim of this study was to investigate in vitro the role of human bone marrow–derived mesenchymal stromal cells (BMSC) and active osteoblasts in control of migration, lodgment, and proliferation of HSCs.

Methodology/Principal Findings

A complex mixed multicellular spheroid in vitro model was developed with human BMSC, undifferentiated or induced for one week into osteoblasts. A clear limit between the two stromal cells was established, and deposition of extracellular matrix proteins fibronectin, collagens I and IV, laminin, and osteopontin was similar to the observed in vivo. Noninduced BMSC cultured as spheroid expressed higher levels of mRNA for the chemokine CXCL12, and the growth factors Wnt5a and Kit ligand. Cord blood and bone marrow CD34+ cells moved in and out the spheroids, and some lodged at the interface of the two stromal cells. Myeloid colony-forming cells were maintained after seven days of coculture with mixed spheroids, and the frequency of cycling CD34+ cells was decreased.

Conclusions/Significance

Undifferentiated and one-week osteo-induced BMSC self-assembled in a 3D spheroid and formed a microenvironment that is informative for hematopoietic progenitor cells, allowing their lodgment and controlling their proliferation.

Infection -> acute and chronic pyelonephritis

 

 

Atherosclerosis related including infarction and renal artery stenosis

 

 

Ocular

 

 

Cataracts

 

 

Glaucoma

 

 

Diabetic retinopathy

 

 

Non-proliferative

 

 

Proliferative

 

 

Macular oedema

 

 

Neuropathy

 

 

Peripheral nerves

 

 

Autonomic nerves

 

 

Mononeuropathy

 

 

Diabetic polyradiculopathy

 

 

Skin

 

 

Ulcers: multifactorial

 

 

Impaired sensation due to neuropathy

 

 

Predisposition to infection

 

 

Impaired blood supply due to atherosclerosis and microangiopathy impairing healing

 

 

Necrobiosis lipoidica diabeticorum (rare)

 

 

Infection

 

 

Predisposition to infection (e.g. pulmonary, urinary tract, skin) related to hyperglycaemia and impaired function of

phagocytes and other inflammatory cells

 

 

 

Liver: non-alcoholic steatosis, steatohepatitis and cirrhosis

 

 

Acute metabolic complications

 

 

Diabetic ketoacidosis (primarily in type 1)

 

 

Non-ketotic hyperosmolar coma (type 2)

 

 

Hypoglycaemia from too much insulin or hypoglycaemics

 

Nephropathy, atherosclerosis, neuropathy, ocular complications

 

Are late complications

 

 

Risk increases in relation to duration of hyperglycaemia

 

 

Usually become apparent in 2nd decade of hyperglycaemia, may be present at time of diagnosis of type 2 which often

has a long asymptomatic period

 

 

 

Better blood glucose control reduces risk

 

 

Other undefined factors modulate the risk e.g. genetic

 

 

Nephropathy, neuropathy, retinopathy are largely related to microangiopathy

 

BACKGROUND HISTOLOGY

Connective tissue

 

Cells include: fibroblasts, myofibroblasts, mast cells, adipocytes, macrophages, undifferentiated mesenchymal cells

 

 

Extracellular matrix

 

 

Fibres

 

 

Collagen, including reticulin

 

 

Elastin

 

 

Ground substance: Glycosaminoglycans bound to proteoglycans

 

 

Structural glycoproteins e.g. laminin, fibrillin

 

 

Tissue fluid

Connective tissue proper: loose and dense

 

Specialised connective tissue e.g. adipose tissue, bone, cartilage

 

 

Basement membranes (BM)

 

Epithelial, endothelial and mesothelial cells sit on a BM

 

 

Similar material surrounds Schwann cells and various other connective tissue cells (e.g. adipocytes, smooth muscle

cells) – termed basal lamina

 

 

 

Composition

 

 

Specialised extracellular matrix

 

 

Central electron dense layer (lamina densa) with less distinct electron lucent layers (lamina rara) on either side (all

3 together sometimes termed basal lamina)

 

 

 

Delicate network of predominantly type IV collagen in a matrix of glycoproteins (e.g. laminin) and other

extracellular components (e.g. heparan sulphate proteoglycan) largely produced by the overlying cells

 

 

 

+/- reticular layer: collagen type III originating from underlying connective tissue cells

 

 

Often too thin to be seen distinctly on H&E with light microscopy except in areas where it is thicker (e.g. trachea)

but can be seen with special stains on light microscopy

 

 

 

Function

 

 

Bonds cells to underlying connective tissue

 

 

Provides framework for cell development and regeneration

 

 

Freely permeable to small molecules but impedes passage of macromolecules

 

Arteries

Layers (general):

 

Intima: endothelium (simple squamous), basement membrane, (+ small amount of connective tissue/elastin in some),

internal elastic lamina (except in smallest arterioles)

 

 

 

Media: variable amounts of smooth muscle and extracellular matrix, predominantly elastin; in some vessels an external

elastic lamina is also present

 

 

 

Adventitia: connective tissue including abundant elastin, vasa vasorum in larger vessels

Media

 

 

 

Large arteries (aorta and it’s main branches): abundant elastic tissue

 

 

Medium (distributing arteries) and small (<2mm) arteries: predominantly smooth muscle

 

 

Arterioles (diam 100um or less): several layers of smooth muscle cells only

Smooth muscle cells produce the extracellular matrix including elastin

 

 

PROPOSED GENERAL MECHANISMS UNDERLYING CHRONIC COMPLICATIONS IN DIABETES:

Complex and not fully understood, different pathways that interact. Genetic factors in the patient also have an important

influence.

 

Hyperglycaemia ->

 

 

Formation of advanced glycation end products (AGE) – glucose binds irreversibly to protein amino groups. AGE may

also form on lipids, nucleic acids.

 

 

 

AGE modified extracellular matrix components

 

 

Lead to protein cross-linking

 

 

Are resistant to proteolytic digestion

 

 

Trap other proteins (e.g. plasma proteins)

 

 

May promote cell damage

 

 

Non-enzymatic glycation of haemoglobin: HbA1c – serves as marker of glycemic control

 

 

May alter intracellular signalling, gene expression and oxygen derived free radical formation

 

 

Increase in aldose reductase pathway

 

 

In cells not requiring insulin for glucose uptake e.g. Schwann cells, retinal pericytes, lens of eye

 

 

Metabolism of excess intracellular glucose -> excessive glucose metabolites (e.g. sorbitol) with reduced synthesis of

an important antioxidant -> osmotic cell injury and increased susceptibility to oxidative injury

 

 

 

Production of reactive oxygen species ->

 

 

Upregulation of growth factor expression e.g. VEGF

 

 

Alteration of proteins and lipoproteins

 

 

Cell damage

 

 

Increased activation of protein kinase C (PKC) signal transduction pathway

 

 

May be related to AGE formation

 

 

Activation of signal transduction pathways for extracellular matrix protein production

 

 

Overactive renin-angiotensin system

 

 

Angiotensin II stimulates production of important growth factors e.g. TGF-beta that plays a role in extracellular

matrix formation in the renal mesangium and VEGF is important in proliferative retinopathy

 

 

 

Important in nephropathy and retinopathy

Understanding pathogenesis helps in the development of potential treatments e.g. use of inhibitors of AGE formation,

 

antioxidants, angiotensin II inhibitors

 

The simplified version

 

 

 

Increased amounts of extracellular matrix with altered structure and function due to:

 

 

Upregulation (various mechanisms) of production of various growth factors and cytokines -> increased extracellular

matrix production

 

 

 

AGE modified extracellular matrix proteins -> cross-linking, plasma protein trapping, reduced proteolytic digestion

 

 

Cell damage e.g. via aldose reductase pathway and osmotic injury, activation of reactive oxygen species

The microangiopathy (capillary basement membrane thickening), hyaline arteriolar changes and mesangial thickening in

 

diabetes are caused by the above processes. Hypertension may play a role in the development of hyaline arteriolosclerosis.

 

 

Normal renal glomerular structure

 

Filtration barrier

 

 

Endothelial cells, epithelial cells and basement membrane

 

 

Endothelium

 

 

Fenestrated with large pores that only prevent blood cells and platelets from passing through

 

 

The diaphragm that typically spans fenestrations between endothelial cells in certain other vascular beds is absent

 

 

Epithelial cells (podocytes)

 

 

Extensive array of processes that interdigitate on outside of capillary with slit like spaces (filtration slits) between

 

 

Each filtration slit is spanned by a thin filtration slit diaphragm or membrane

 

 

Glomerular capillary basement membrane (BM) of central importance

 

 

Made by epithelial and endothelial cells

 

 

Composed of collagen type IV, glycoproteins and proteoglycans

 

 

No reticular component

 

 

Size barrier: molecules larger than about 69,000 daltons unable to cross

 

 

Charge barrier: proteoglycan component is anionic (negatively charged), therefore repels negatively charged

molecules

 

 

 

Albumin has a molecular weight of 69,000 daltons and is negatively charged

 

 

Mesangium

 

 

Mesangial cells and extracellular matrix (various collagens and ground substance)

 

 

Function

 

 

Supports capillary loops

 

 

Cells have phagocytic function and clean the basement membrane

 

 

May regulate blood flow in capillaries

 

Diabetic nephropathy

 

A clinical syndrome in patients with diabetes mellitus characterised by persistent microalbuminuria, worsening proteinuria,

hypertension and progressive deterioration in renal function. The pathological correlate of diabetic nephropathy is diabetic

 

glomerulosclerosis characterised by a progressive increase in extracellular matrix in the mesangium and capillary basement

 

membranes.

 

 

 

Approximately 25-35% of patients with longstanding diabetes (types 1 and 2) develop diabetic nephropathy and renal failure.

 

 

Diabetic retinopathy often also present, especially in type 1 diabetes

 

 

Clinical and pathological features and progression

 

 

Early:

 

 

Initial increased intraglomerular pressure with hyperfiltration, potentially at least partly related to vasoconstrictor

effect of angiotensin II on efferent arterioles, associated with enlarged glomeruli, commencing within first few years

 

of onset

 

 

 

Microalbuminuria appears 5–10 years after the onset of diabetes

 

 

Later

 

 

Onset of overt proteinuria (10-15 years or more after diabetes onset) +/- nephrotic syndrome +/- hypertension,

beginning deterioration in renal function.

 

 

 

Diffuse and nodular diabetic glomerulosclerosis

 

 

Diffuse

 

 

Diffuse thickening of glomerular capillary BMs (not seen on light microscopy until very thickened)

 

 

Diffuse increase in mesangial matrix +/- mild proliferation of mesangial cells

 

 

Nodular (Kimmelstiel-Wilson lesion)

 

 

Localised nodular areas of increased mesangial matrix with few cells

 

 

Less common than diffuse and generally superimposed on diffuse lesion

 

 

Insudative glomerular lesions: Eosinophilic nodular accumulations of plasma constituents in capillary loops or in

Bowmans capsule

 

 

 

Hyaline arteriolosclerosis in both afferent and efferent arterioles

 

 

Tubular basement membrane thickening

 

 

Immunofluorescence: non-specific (not immunologic) trapping of plasma albumin and IgG in tubular and capillary

basement membranes

 

 

 

Most of the changes are not specific for diabetes

 

 

Mesangial and glomerular capillary BM thickening related to excessive and altered extracellular matrix:

pathogenesis involves accumulation of AGE products, upregulation of growth factors

 

 

 

Glomerular changes -> narrowing of capillary lumina and glomerular ischaemia, hyaline arteriolosclerosis

contributes to glomerular ischaemia.

 

 

 

Hypertension can contribute to glomerular injury.

 

 

Later still: Falling GFR: damaged glomeruli -> impaired renal function. Progressive irreversible glomerulosclerosis,

related tubules atrophy (no blood flow into efferent arterioles and peritubular capillaries) and interstitial tissue undergoes

 

fibrosis -> further impairment of renal function

 

 

 

End stage renal disease: 5-10 years after development of overt proteinuria (or 10-20 years after onset of

microalbuminuria), however, there is considerable variability between patients. Macroscopically the kidneys may be

 

slightly enlarged with a granular surface, or small due to co-existent changes related to hypertension or chronic

 

pyelonephritis.

 

 

 

Pathogenesis of diabetic glomerulosclerosis: complex, at least partly related to microangiopathy (pathogenesis outlined

above)

 

Various pathways implicated, pathways interact

 

 

 

Haemodynamic factors

 

 

Hyperglycaemia -> glomerular hyperfiltration and microalbuminuria, altered tubuloglomerular feedback

 

 

Vasoconstrictor effect of angiotensin II more potent on efferent arteriole -> increased glomerular capillary pressure

and filtration

 

 

 

Hypertension may contribute via glomerular hyperfiltration and endothelial and mesangial damage due to

haemodynamic stress

 

 

 

Metabolic factors e.g. AGE mechanism, activation of protein kinase C

 

 

Hormonal factors: overactive intrarenal renin angiotensin system (RAS), also contributes to development of

hypertension.

 

Effects of angiotensin II in kidney

 

 

 

Sodium and water retention by tubules

 

 

Can activate other cytokine pathways such as transforming growth factor-beta (TGF-beta) and platelet derived

growth factor (PDGF) systems. TGF-beta-1 stimulates an increase in mesangial matrix deposition and glomerular

 

basement membrane (GBM) thickening

 

 

 

Impairs nitric oxide function which has vasodilatory and protective role

 

 

Can downregulate nephrin, an important protein of the slit diaphragm, leading to proteinuria

 

 

Genetic influences

 

 

Clinical

Progression slowed by good blood glucose control, strict blood pressure control, administration of ACE inhibitors or

 

angiotensin receptor blockers (ARBs) and treatment of dyslipidemia.

 

 

 

Proteinuria and nephrotic syndrome

 

 

Structural alterations in and loss of negative charge of glomerular capillary BM allow albumin to pass through

 

 

Albuminuria is a marker of greatly increased cardiovascular morbidity and mortality for patients with either type 1 or

type 2 diabetes

 

 

 

Hypertension in diabetics

 

 

From diabetic nephropathy

 

 

From chronic renal failure

 

 

Other risk factors e.g. obesity, familial

 

 

Renal artery stenosis (less common)

 

 

Chronic renal failure (CRF)

 

 

Diabetic glomerulosclerosis and hyaline arteriolosclerosis -> chronic glomerular ischaemia -> glomerular

obsolescence/sclerosis and also chronic renal ischaemia with tubular atrophy and interstitial scarring -> poorly

 

functioning kidneys

 

 

 

Approx. 30% of patients develop chronic renal failure

 

 

Chronic pyelonephritis and hypertension may also cause/contribute to CRF

Remember also that diabetics can get other renal diseases.

 

 

Ocular complications

 

Cataracts: from lens swelling and opacity

 

 

Glaucoma: formation of fibrovascular membranes on iris related to ischaemia (from microangiopathy) -> blockage of

outflow channels of aqueous humour

 

 

 

Diabetic retinopathy

 

 

Develops in about 75% within 15 years of disease onset

 

 

More prevalent among patients with type 1 diabetes than type 2

 

 

Often coexists with diabetic nephropathy, but they can also occur independently of each other

 

 

Non-proliferative: microvascular changes with pericyte and also ultimately endothelial cell loss, leads to increases in

vascular permeability, vascular weakening and alterations in retinal blood flow, including blockage of capillaries ->

 

exudates, haemorrhages, microaneurysms, microinfarcts

 

 

 

Macula oedema

 

 

Proliferative: ischaemia from microvascular changes -> proliferation of small vessels, initially on surface of retina

and later into the vitreous -> haemorrhages, fibrosis and retinal detachment.

 

 

 

Increased VEGF expression, contributed to by hypoxia and oxidative stress is important in pathogenesis of

proliferative retinopathy

 

 

 

VEGF is an angiogenic growth factor and increases vascular permeability

 

Neuropathy

 

Distal symmetric sensory or sensorimotor neuropathy

 

 

Symmetric, motor and sensory

 

 

?from Schwann cell injury -> demyelination

 

 

?from axonal injury

 

 

?from microangiopathy impairing blood flow and nutrition of nerve

 

 

Autonomic neuropathy

 

 

-> impotence, bowel and bladder dysfunction etc

 

 

?similar pathogenesis

 

 

Diabetic polyradiculopathy

 

 

Severe disabling pain in the distribution of one or more nerve roots

 

 

May be accompanied by motor weakness

 

 

Focal or multifocal asymmetric neuropathy/mononeuropathy

 

 

Affects larger nerves

 

 

?from microangiopathy impairing blood flow and nutrition of nerve

 

Atherosclerosis

 

Slow build up over years of lipids and fibrous material in the intima of large and medium sized arteries

 

 

In diabetics may extend more distally than usual

 

 

Pathogenesis in diabetes

 

 

Vascular basement membrane and endothelial changes -> increased permeability, trapping of lipids in intima

 

 

Dyslipidaemia

 

 

Hypertension

 

Sources

Anthony S. Fauci, Eugene Braunwald, Dennis L. Kasper, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, and Joseph

Loscalzo, Eds. Harrison’s online: Harrison’s Principles of Internal Medicine, 17th Edition. The McGraw-Hill Companies.

Ahmed N. Advanced glycation endproducts—role in pathology of diabetic complications. Diabetes Research and Clinical

Practice 2005: 67: 3–21

Caldwell RB, Bartoli M, Ali Behzadian M, El-Remessy AEB, Al-Shabrawey M. Platt DH, Caldwell RW. Vascular endothelial

growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev

2003; 19: 442–455.

D’ Agati VD, Jennette JC, Silva FG. Non-Neoplastic Kidney Diseases. 2005. American Registry of Pathology Press.

Jawa A, Kcomt J, Fonseca VA. Diabetic nephropathy and retinopathy. Med Clin N Am 2004: 88: 1001–1036

Kumar V, Abbas AK, and Fausto N. Robbins and Cotran Pathologic Basis of Disease. 7th edition, 2005. Elsevier Saunders.

Rubin E, Gorstein F, Rubin R, Schwarting R and Strayer D. Rubin’s Pathology Clinicopathologic Foundations of Medicine. 4

 

th

 

edition, 2005. Lippincott Williams and Wilkins

Tsilibary E.C. Microvascular basement membranes in diabetes mellitus. J Pathol 2003; 200: 537–546.

Wilkinson-Berka JL. Angiotensin and diabetic retinopathy. The International Journal of Biochemistry and Cell Biology 2006:

38:752-765


Morphology of Reversible Cell Injury and Necrosis

Cellinjury

  • Two processes cause the basic changes of necrosis: denaturation of proteins, and enzymatic digestion of organelles and cytosol.
  • Autolysis indicates digestion by lysosomal enzymes of the dead cells themselves
  • The necrotic cell is eosinophilic and glassy, maybe vacuolated. The membranes are fragmented. Nuclear changes include pyknosis (small, dense nucleus), karyolysis (faint, dissolved nucleus) and karyorrhexis (broken into bits)
  • Types of necrosis include:
    • coagulative (myocardium, kidney, liver – usually ischaemic)
    • liquefactive (brain and abscesses – autolysis and heterolysis dominate)
    • caseous (tuberculous – soft and cheesy cell debris)
    • fatty (adipose – actions of lipases that decompose triglycerides that complex with calcium to form soaps)

Apoptosis

  • Morphological features include cell shrinkage, chromatin condensation and fragmentation, formation of cytosolic blebs and apoptotic bodies, phagocytosis of apoptotic bodies by adjacent healthy cells or macrophages, and a conspicuous lack of inflammation
  • In many instances, it is dependent on gene activation
  • Occurs in the following settings:
    • programmed cell destruction during embryogenesis
    • hormone-dependent involution (eg. endometrium)
    • cell depletion in proliferating populations
    • pathological atrophy in parenchymal organs after duct obstruction
    • cell death by cytotoxic T cells
    • cell injury from some viral diseases
    • mild traumatic insult

Cellular Adaptation to Injury

  • Atrophy = shrinkage in size by the loss of cell substance
    • causes include decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, aging
    • diminished function but not dead – autophagy, reduced organelles, increased number of autophagic vacuoles; components resisting digestion are deposited as lipofuscin granules, giving a brown appearance
  • Hypertrophy = increase in the size of cells (but not their number)
    • causes include increased functional demand, hormonal stimulation
    • triggered by cell membrane interactions and mechanical factors
  • Hyperplasia = increase in the number of cells
    • can be physiologic (endometrial proliferation, hyperplasia of the liver after lobectomy) or pathologic (almost always excessive hormonal stimulation)
    • when the stimulus is removed, the hyperplasia disappears – this is a crucial difference from neoplasia
  • Metaplasia = a reversible change in which one cell type is replaced by another
    • examples include Barretts’ oesophagus, the respiratory tract of smokers
    • thought to occur from genetic reprogramming

Subcellular Responses

  • Lysosomes are involved in digestion of ingested materials through autophagy and heterophagy. It is pronounced in cells undergoing atrophy. Lysosomes with indigestible material may persist within cells or be extruded.
  • Hypertrophy of the smooth ER, such as by barbiturates, increasing the surface area available for mixed-function oxidase pathway.
  • Mitochondrial alterations, in size, number and function.
  • Cytoskeletal abnormalities, which impede transport of organelles and molecules. The basic cell architecture can be disrupted.
  • Induction of heat shock proteins. These play a role in normal intracellular protein housekeeping (eg. folding them). They are thought to be induced to refold damaged proteins or to tag them for destruction (ubiquitin).
  • Intracellular accumulations – fats (steatosis), cholesterols (atheroma), proteins (Mallory body in alcoholic hepatocytes), glycogen (diabetic renal tubular epithelium), pigments (anthracosis).
  • Pathologic calcification, which implies the abnormal deposition of calcium salts in soft tissues. Dystrophic calcification occurs in nonviable tissue, where metastatic calcification is deposition of calcium salts in vital tissues and is associated with hypercalcaemia (hyperparathyroidism, hypervitaminosis D, sarcoidosis, Addison’s disease, hyperthyroidism, bone cancers).
  • Hyaline change, intracellularly or extracellularly. This is deposition of proteinaceous material that stains a glassy-pink on H&E.
What are the  Diabetic OPN cells ?
 
 
 
 
 
Whate are the   LT-HSCs ?
 
  • Diabetes impairs the interactions between long-term hematopoietic stem cells and osteopontin-positive cells in the endosteal niche of mouse bone marrow
    Hironori Chiba, Koji Ataka, Kousuke Iba, Kanna Nagaishi, Toshihiko Yamashita, Mineko Fujimiya
    October 1, 2013
  • Human-induced pluripotent stem cell-derived cardiomyocytes for studies of cardiac ion transporters
    Michael Fine, Fang-Min Lu, Mei-Jung Lin, Orson Moe, Hao-Ran Wang, Donald W. Hilgemann
    September 1, 2013
  • Functional expression of smooth muscle-specific ion channels in TGF-β1-treated human adipose-derived mesenchymal stem cells
    Won Sun Park, Soon Chul Heo, Eun Su Jeon, Da Hye Hong, Youn Kyoung Son, Jae-Hong Ko,Hyoung Kyu Kim, Sun Young Lee, Jae Ho Kim, Jin Han
    August 15, 2013
  • Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction
    Bryon R. McKay, Daniel I. Ogborn, Jeff M. Baker, Kyle G. Toth, Mark A. Tarnopolsky, Gianni Parise
    April 15, 2013
  • Autophagy in endothelial progenitor cells is cytoprotective in hypoxic conditions
    Hai-Jie Wang, Dan Zhang, Yu-Zhen Tan, Ting Li
    April 1, 2013
    SOURCE
    • in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells
      Xia Guo, Steven L. Stice, Nolan L. Boyd, Shi-You Chen
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

The

The many cells that make up the blood and immune system

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Driwan stem cell information center(continiu)

FOUNDER
 
Dr Iwan Suwandy,MHA
more infocontact
iwansuwandy@ gmail.com
all free of charge
this info to all human in the world
with
 
THE MIGHTY GOD BLESS
 
 
CELL
 
lets we look
how wonderfool and exciting
 
the mighty GOD CREATION
CELL NOT THE SMALLEST P;ART OF OUR BODY BUT
THE BIGGER IMPORTANCE PART OF OUR REGRERATIVE POTIAL
LOOK AND LEARN CAREFULLY
MANY APPARART INSIDE CELL
 
 
 
CELL CONSIST
 
CELL MEMBRANE
with microvilli,
phagocyte vesicle,
cillia and secrotory villia
 
CYTOPLASM
vesicles
peroxisomes
lysosome
lysosome fusin with incoming phagocyte vesicle
mitochondria
free rebosome
golgi apparatus
microtubule network
centrosome and centriole
 
ROUGH ENDOPLASMIC RETICULYM
 
NUCLEUS
 
inside found
NUCLEOLI
 
INSIDE THE APPARAT CONSIST MANY CHEMICAL WHICH
CONTROL OUR REGRENATIVE FUNCTION TO PROTECT OUR CELL FROM
INTERNAL OR EXTERNAL EXPOSUE
CALL
DNA
CCONSIST
 
 
 
 
AGTC
 
ADENINE
 
GUANINE

Thymine

“Thymine (T, Thy)”  

Thymine Structure

Thymine

In our body’s cells, Thymine (T, Thy) is a Pyrimidine derivative, one of the Nitrogenous Bases (Nucleobases) in the Nucleic Acid (Polynucleotide) of DNA. 

Thymine (5-methyluracil)

Thymine (T) is also known as (5-methyluracil).

 

“Thymine → Uracil”  

 

Thymine (T) is also known as (5-methyluracil) and may be derived by methylation of Uracil (U) at the 5th carbon.

 
 

 
THYMINE
 
CYSTOSINE
 
 
FIVE CHEMICAL CHAINS
 
MILLION EXIST
 
 
STILL IN RECSEARXH TO BUILT
 
 
THE HUMONGENOM
 

he human genome is the complete set of genetic information for humans (Homo sapiens).

This information is encoded as DNA sequences within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. Human genomes include both protein-coding DNA genes and noncoding DNAHaploid human genomes (contained in egg and sperm cells) consist of three billion DNA base pairs,

while diploid genomes (found in somatic cells) have twice the DNA content. While there are significant differences among the genomes of human individuals (on the order of 0.1%), these are considerably smaller than the differences between humans and their closest living relatives, the chimpanzees (approximately 4%[1]) and bonobos.

Genomic informations
Karyotype.png

Graphical representation of the idealized human diploid
karyotype, showing the organization of the genome into chromosomes.
This drawing shows both the female (XX) and male (XY) versions of the
23rd chromosome pair. Chromosomes are shown aligned at their

centromeres. The mitochondrial DNA is not shown.

 NCBI Genome Id.   51
 Ploidy.   diploid
 Genome size.   3,234.83 Mb
 Number of chromosomes.   23 pairs  

The Human Genome Project produced the first complete sequences of individual human genomes. As of 2012, thousands of human genomes have been completely sequenced, and many more have been mapped at lower levels of resolution. The resulting data are used worldwide in biomedical scienceanthropologyforensics and other branches of science. There is a widely held expectation that genomic studies will lead to advances in the diagnosis and treatment of diseases, and to new insights in many fields of biology, including human evolution.

Although the sequence of the human genome has been (almost) completely determined by DNA sequencing, it is not yet fully understood. Most (though probably not all) genes have been identified by a combination of high throughput experimental andbioinformatics approaches, yet much work still needs to be done to further elucidate the biological functions of their protein and RNA products. Recent results suggest that most of the vast quantities of noncoding DNA within the genome have associated biochemical activities, including regulation of gene expression, organization of chromosome architecture, and signals controlling epigenetic inheritance.

The haploid human genome contains approximately 20,000 protein-coding genes, significantly fewer than had been anticipated.[2][3]Protein-coding sequences account for only a very small fraction of the genome (approximately 1.5%), and the rest is associated with non-coding RNA molecules, regulatory DNA sequencesLINEsSINEsintrons, and sequences for which as yet no functionhas been elucidated.[4]

 
AND
 
 
RNA
IF THE SYSTEM CANNOT REVANCE ADAINS THE EXPOSURE WE BECAME SICK AND OUR CELL AND THE SYSTEM BECAM DAMGE FASTLY BECAME ACUTE DISEASE
AND SLWLY BECAME CHRONIC DISEASE
WHEM W WE SURVIVE AND BECAME OLDER
THE SYSTEMIC STARTING TO DEGRETIV AGING
WE MUST PROTECT WITH
STEM CELL OR GENETIC REGERATION
 
 
 gen therapy more difficullt
 
like many years research still not many found like indonesian eijkman lab by prof DR Sangkot done
 
better to used
stem cell
 
is basically any cell that can replicate and differentiate.
This means the cell can not only multiply,
it can turn into different types of tissues.
 
 
There are different kinds of stem cells.

All Stem Cells Have Three Main Properties:

1. They can divide and renew themselves for extended periods of time.

2. They can morph into specialized cell types.

LIKE

cancer stem cell

liver ca stem cell

 

skin stem cell control eilepsy

 

 hemopoetic stem cell

pancreas stem cell

renal stem cell

 

cardiac stem cell

 

3. They are unspecialized (which allows them to be a blank slate for morphing into specialized cells).

There are three main types of stem cells and, depending on the source, they are all harvested differently.

1. “embryonic stem cell.”

 
 
 
Most people are familiar with or have heard the term “embryonic stem cell.”
 
These are cells from the embryonic stage
 
2the “pluri-potential” cells
 
 
 
that have yet to differentiate – as such, they can change into any body part at all.
 
These are then called “pluri-potential” cells.
Because they are taken from unborn or unwanted embryos, there has been considerable controversy surrounding their use.
 
3.the “adult stem cell.”
 
 
Another kind of stem cell is the “adult stem cell.”
 
This is a stem cell that already resides in one’s body within different tissues.
 
a. In recent times, much work has been done isolating bone-marrow derived stem cells.
 
b.These are also known as
 
 
 
“mesenchymal stem cells”
because they come from
1) the mesodermal section of your body.
 
2)They can differentiate into
a)bone and cartilage,
b)and probably all other mesodermal elements,
such as
(1) fat tissue
(2), connective tissue
(3), blood vessels,
(4) muscle
(5) and nerve tissue.
 
hemopoetic stem ceel
 
 
 
 
 
WHAT WERE THE DFFERENCE BETWEEN  EMBRIONIC  AND ADULT STEM CELL?
 
 
 
A.DIFFERENT EXPANTION
 
1) EMBRYONIC STEM CELL
WHOLE BONE MARROW  DERIVED NESENCHYMAL,HEMOPOETIC AND ENDOTHELIA PROGENITOR TRANSCRIPT FACTOR MICRO RNA’S REPROGRAMMING(B) TO REPAIR CELL
 
2)ADULT STEM CELL
 
BISIDE EMBRYONIC STEM CELL
PLUS ADDED HUMORAL FACTOR HOMING(D) TO REPAIR CELL
1)CIRCULATING STEM CELL
2)RESIDENT STEM CELL
3)FIBROBLAST
 
 
 
WHAT IS THE PROBLEM OF STEM CELL THERAPY?
 

This will depend on the type of degenerative condition you have.

A specialist will evaluate you and discuss whether you’re a potential candidate for stem cell therapy.

If after you’ve been recommended for treatment, had an opportunity to understand the potential risks and benefits, and decided on your own that you would like to explore this avenue of treatment, then you can be considered for treatment.

Of course, even though it’s a minimally invasive procedure, you will still need to be medically cleared for the procedure.

a potential candidate for stem cell therapy.

Stem Cell Therapy For Joint And Soft Tissue Injuries

Stem Cells Therapy Is Helping People With Their Golf Game

Dr. Brandt is one of a select few physicians in the country to be trained in a groundbreaking, minimally invasive technique that is saving many patients from undergoing difficult joint replacement surgery. 

Stem cell therapy relies on the body’s own natural healing abilities to repair tissue in affected joints. This technique begins by taking a patient’s own stem cells found in adipose (fat) tissue, concentrating the cells into a small injection, and then reintroducing them into the area of concern.

This process stimulates the body to repair and replace tissue that has disintegrated over time or been traumatized from injury or overuse.

 

How does Adult Stem Cell Therapy work ?

Cell therapy is simply helping your body do what is does naturally.

If you get a cut on your skin, stem cells in your blood go to that cut. They lodge in the damaged tissue and receive signals from the adjacent damaged tissue.

The stem cell responds

by sending out it own signals to the body.

It requests materials,

like proteins,

to rebuild what was damaged,

to regenerate the tissue,

the natural healing process.

Modern stem cell therapy is the process of finding the adult stem cells that are best at repairing specific damaged tissue, be it vascular, heart, neurological, pancreas, etc.

These specific cells are isolated in the lab, cultured, multiplied and activated.

They are your repair cells, your DNA and know how to fix you.

Then the doctor puts them back into your body, targeted to the damaged tissue.

This can be by IV, direct injection into the heart muscle, direct injection into damaged spinal cord, direct injection into the pancreas or direct injection into the area of the brain damaged by stroke.

The stem cells can do two things. Differentiate and mature into that type of tissue – a nerve cell, heart muscle, cartilage or whatever.

They can also help support other cells resident in that tissue to mature into healthy cells. In some case both situations may occur. This process is still being investigated and holds the key to future medical treatments. One thing for sure is that adult stem cell therapy is being used today to treat somebody with a similar condition you are concerned about. Contact us and we can help guide you to the best available therapy today

Is Adult Stem Cell Therapy safe ?

Yes, autologous stem cell procedures for adult stem cell therapy are totally safe as the cells come from your own body.

There cannot be any problems of rejection because they carry the patient’s own DNA.

 

How are the stem cells taken from the body and what happens ?

A small amount of tissue is taken from bone marrow, blood, fat, or skin.
The procedure is simple and minimally invasive.
This sample is then sent to a laboratory where the stem cells that are needed are isolated and harvested into the many millions that are required to be therapeutically effective.
 

How did I feel after treatment ?

Stem cell therapy is your body repairing itself. Immediately after treatment patients usually feel the same, maybe a little more optimistic about their recovery. Again, depending on your condition, for some neurological conditions patients have seen improvement in a matter of days and felt better. For example, slurred speech improvement or tremors. Doctors will tell patients the body usually takes 3-6 months for cellular repair activity to take place in damaged tissue or organs. Check out what patients have to say that have your condition.
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Driwan Stem CEll THERAPY INFORMATION CENTER (CONTINIU)

 

FOUNDER
 
Dr Iwan Suwandy,MHA
more infocontact
 
iwansuwandy@ gmail.com
all free of charge
this info to all human in the world
with
 
THE MIGHTY GOD BLESS
 
 

Mast cell homeostasis: a fundamental aspect of allergic disease

JJ Ryan, M Kashyap, D Bailey… – Critical Reviews™ in …, 2007 – dl.begellhouse.com
 One also wonders if part of the clinical efficacy of anti-IgE therapy is related to regulat- ing mast
cell life span  TGF-β1 has been shown to inhibit IL-3-depen- dent proliferation of peritoneal mast
cells and BMMC.92,93 In addition, TGF-β1 inhibited stem cell factor-mediated 

Reversing breast cancer stem cell into breast somatic stem cell

L Wijaya, D Agustina, AO Lizandi… – Current …, 2011 – ingentaconnect.com
 Tel: +62 21 47860173/57869756; Fax, +62 21 47860180; E-mails: fsandra@sci-indonesia.org;
ferrysandra  In this regard, several groups have studied the capability of embryonic stem cell
micro- environments to reprogram the phenotype of cancer cells [49]. 

Dihydroartemisinin-piperaquine versus chloroquine in the treatment of Plasmodium vivax malaria in Thailand: a randomized controlled trial

AP Phyo, KM Lwin, RN Price… – Clinical infectious …, 2011 – cid.oxfordjournals.org
 island of New Guinea [4–6]. The degree of CQ resistance in Papua, Indonesia and Papua  More
recently, CQ-resistant P. vivax has been documented across the Indonesian archipelago [1] and
in  1% packed red blood cells, as the number of parasites per 500 white blood cells

Hungary detains 4 over illegal stem cell treatment

K Than, MOA Boy, I Shock – Reuters, available at, 2009 – stemcellresearchnews.com
 “Nowhere in the world is this used as therapy and on a  It said only Hungary’s Healthcare Scientific
Council has the authority to issue permission to conduct stem cell research.  Stem cells are the
body’s ‘master cells‘, the source of all cells and tissue, including brain, blood, heart 

… and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South Sumatra, Western Indonesia: an open-label, …

I Sutanto, S Suprijanto, A Kosasih… – Clinical infectious …, 2013 – cid.oxfordjournals.org
 All treatment doses were given as directly observed therapy by the healthcare attendants.  in the
study, and fulfilled standards for good manufacturing practices in China and Indonesia,
respectively.  and expressed per microliter assuming a leukocyte count of 8000 cells/µL blood. 

Evaluation of crucial factors for implementing shed-microspore culture of Indonesian hot pepper (< i> Capsicum annuum</i> L.) cultivars

EDJ Supena, W Muswita, S Suharsono… – Scientia horticulturae, 2006 – Elsevier
 anther-culture-derived potato plants (Singsit and Veilleux, 1991) and of regenerated cell- and
tissue  We used also other Indonesian large type hot pepper varieties ‘Gada’, ‘Prabu’ and  which
were grown in the breeding company East West Seed Indonesia (EWINDO) Purwakarta 

Survey and analysis of satellite-based telemedicine projects involving Japan and developing nations: investigation of transmission rates, channel numbers, and node …

I Nakajima, M Natori, M Takizawa… – Studies in health …, 2001 – IOS Press
 program exchange, the National Kumamoto Hospital provided a program on adult T-cell leukemia
to Indonesia, while the Indonesian Unjani Hospital  Detailed information on bone-marrow stem
cell transplants is provided by the Medical Information Department of Shinshu 

Acquired sideroblastic anaemia after aplastic anaemia caused by D-penicillamine therapy for rheumatoid arthritis.

AC Ramselaar, AW Dekker, O Huber-Bruning… – Annals of the …, 1987 – ard.bmj.com
 Case report A 68 year old Indonesian man had a five year history of seropositive  there was a
moderately active toxic granulopoiesis with a left shift and sporadic blast cells with rheumratoid
arthritis.’ In these reports, hoxever,there were no fealtures of stem cell injury such as the 

[PDF] Smenospongine, a sesquiterpene aminoquinone from a marine sponge, induces G1 arrest or apoptosis in different leukemia cells

D Kong, S Aoki, Y Sowa, T Sakai, M Kobayashi – Marine drugs, 2008 – mdpi.com
 smenospongine, a sesquiterpene aminoquinone, from the Indonesian marine sponge
Dactylospongia elegans.  Smenospongine was isolated from the marine sponge Dactylospongia
elegans (collected in Indonesia in 2001) as described previously [12].  Stem Cells Dev. 

Runx2, p53, and pRB status as diagnostic parameters for deregulation of osteoblast growth and differentiation in a new pre‐chemotherapeutic osteosarcoma cell line ( …

BP Pereira, Y Zhou, A Gupta, DT Leong… – Journal of cellular …, 2009 – Wiley Online Library
 osteosarcoma cell lines (OS1, OS2 and OS3) were developed from bone tumour biopsies from
patients of, respectively, Singaporean Chinese (OS1) and Indonesian Chinese (OS2  To examine
the phenotypic state of OS1 cells from a mesenchymal stem cell perspective, we 

Combined radiotherapeutic and surgical management of a spinal cord compression by extramedullary hematopoiesis in a patient with hemoglobin E beta-thalassemia

KH Shin, S Sharma, SJ Gregoritch, RM Lifeso… – Acta …, 1994 – karger.com
 a pale, jaundiced 22-year-old male of mixed Dutch-Indonesian heritage presented  A), with
decreased red cell production, microcytosis and decreased red cell survival.  as erythrocytes and
granulocytes, are relatively radioresistant, mitotic cells (especially stem cells) are highly 

Increased cell viability and proliferation in post-hypoxic hippocampal tissue culture treated with Acalypha indica root extract

S Yolanda, EW Bachtiar, N Ibrahim – Medical Journal of Indonesia, 2011 – mji.ui.ac.id
 of Physiology, Faculty of Medicine University of Indonesia and Department of Oral Biology, Faculty
of Dentistry University of Indonesia for their  New hope for stroke patients: mobilization of
endogenous stem cells Haas S, Weidner N, Winkler J. Adult stem cell therapy in stroke. 

The effect of type 2 diabetes mellitus on the presentation and treatment response of pulmonary tuberculosis

B Alisjahbana, E Sahiratmadja… – Clinical Infectious …, 2007 – cid.oxfordjournals.org
 5,6,7,8–9]. We have confirmed the association between DM and TB in Indonesia, which has  In
the era before insulin therapy, patients with DM appeared to be doomed to die of  In a prospective
cohort study in an Indonesian region, we examined whether DM was associated with 

Non-bacterial infections in Asian patients treated with alemtuzumab: a retrospective study of the Asian Lymphoma Study Group

SJ Kim, JH Moon, H Kim, JS Kim… – Leukemia & …, 2012 – informahealthcare.com
 graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplant
(HSCT  who received alemtuzumab plus ICE chemotherapy (ifosfamide, carboplatin, etoposide)
in Indonesia A-DHAP) is effective for relapsed peripheral T-cell lymphoma, unspecified 

[HTML] Quality of life during active treatment for pediatric acute lymphoblastic leukemia

L Sung, R Yanofsky, RJ Klaassen, D Dix… – … Journal of Cancer, 2011 – Wiley Online Library
 ALL: acute lymphoblastic leukemia; CI: confidence interval; SCT: stem cell transplantation; QoL 
two dexamethasone-based protocols named the Wijaya Kusuma and Indonesia ALL protocols. 
Health-related quality of life assessment in Indonesian childhood acute lymphoblastic 

Cell-based screen for antimitotic agents and identification of analogues of rhizoxin, eleutherobin, and paclitaxel in natural extracts

M Roberge, B Cinel, HJ Anderson, L Lim, X Jiang, L Xu… – Cancer research, 2000 – AACR
 NCI Natural Products Repository extract N29701 was obtained from the stem bark of the tree
Ilex macrophylla in Kalimantan, Indonesia Rhizoxin is very cytotoxic to cancer cells in vitro or
in mice (20 , 30) , including cell lines resistant to the Vinca alkaloids (30) . 

SIOP‐PODC recommendations for graduated‐intensity treatment of retinoblastoma in developing countries

G Chantada, S Luna‐Fineman, RS Sitorus… – Pediatric blood & …, 2013 – Wiley Online Library
 University of Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. 5  However, when
a single aspiration fails to show malignant cells, a more exhaustive bone marrow  with stage IV
disease benefit from more intensive chemotherapy with autologous stem cell rescue 26. 

[PDF] Bone marrow-derived stem cells as an adjunctive treatment for acute myocardial infarction: a systematic review and meta-analysis

RA Kuswardhani, A Soejitno – Acta Med Indones, 2011 – inaactamedica.org
 Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia 2. Wollert KC, Drexler H.
Cell therapy for the treatment of coronary heart disease: a critical appraisal.  3. Leri A, Kajstura
J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration. 

Doxycycline Treatment of Brugia malayi—Infected Persons Reduces Microfilaremia and Adverse Reactions after Diethylcarbamazine and Albendazole Treatment

T Supali, Y Djuardi, KM Pfarr… – Clinical infectious …, 2008 – cid.oxfordjournals.org
 Twelve months after the commencement of doxycycline therapy, there was an almost complete 
This European Union—funded collaborative study of European and Indonesian institutions was 
by the Commission of Medical Ethics of the University of Indonesia (Jakarta, Indonesia 

Disfiguring generalized verrucosis in an indonesian man with idiopathic CD4 lymphopenia

B Alisjahbana, R Dinata, E Sutedja… – Archives of …, 2010 – archderm.jamanetwork.com
1.

Dusko Ilic explores the latest developments in the field of stem cell research and regenerative medicine

D Ilic – 2008 – Future Medicine
 CordLife (www.cordlife.com), which currently has operations in ten countries, and Indonesian
pharmaceutical giant  However, that will not be the case in Indonesia’s highly seg- mented market
and the  and an annual fee of US$130 will be beyond the means of most Indonesians

[PDF] Climate talks focus on lesser goals

J Tollefson – Nature, 2010 – environmentportal.in
 Indonesia recently announced plans to reduce its emissions by 26% by 2020 com- pared with
predicted levels if emissions were left  cells was difficult for a while, there has been an upsurge
in the commercialization of adult stem cells, with several stem-cell therapies now in 

Autologous recovery with protractedly undetectable donor chimerisms can precede stable donor engraftment in a nonmyeloablative cord blood transplant

WHY Khee, PTH Chye, TC Hoe, HG Fung… – International journal of …, 2003 – Springer
 posttransplantation but developed pneumo- nia 8 months later after he had returned to his home
in Indonesia cord blood transplantation for treating multiple myeloma in which an absence of
detectable donor cells by VNTR analy- sis 4 weeks after stem cell infusion was 

[PDF] US Food and Drug Administration international collaborations for cellular therapy product regulation

JA Arcidiacono, JW Blair… – … cell research & therapy, 2012 – biomedcentral.com
 including Australia, Canada, China (Hong Kong), Chinese Taipei the European Union, Indonesia,
Japan, Pan  This article is part of a thematic series on Clinical applications of stem cells edited
by  Stem Cell Research & Therapy 2012, 3:38 http://stemcellres.com/content/3/5/38 

Key gaps in the knowledge of< i> Plasmodium vivax</i>, a neglected human malaria parasite

I Mueller, MR Galinski, JK BairdJM Carlton… – The Lancet infectious …, 2009 – Elsevier
 of vivax malaria as relatively benign compared with falciparum malaria might stem in part  32 The
risk of therapeutic failure drops as you move north across western Indonesia and into  is a
substantial threat to health on the Malaysian peninsula, the Indonesian archipelago, and 

[PDF] Pharmacogenetic application in personalized cancer treatment

H Kristyanto, AR Utomo – Acta Med Indones, 2010 – inaactamedica.org
 Jl. Salemba 6 Jakarta Pusat 10430, Indonesia. ** Stem Cell and Cancer Institute, Jakarta.  Mutations
in the KRAS gene are found in approximately 15 to 30% of patients with non-small cell lung cancer
(NSCLC) and 40 to 45% of patients with MCRC, and their presence typically 

Idiopathic CD4 lymphocytopenia

UA Walker, K Warnatz – Current opinion in rheumatology, 2006 – journals.lww.com
 of review: A severe decrease of CD4 T cells predisposes humans to opportunistic infections.
In adults, HIV is certainly the most common cause of CD4 lymphocytopenia, but other causes,
such as infections, autoimmune diseases, immunosuppressive therapy, lymphoma and 

End points for testing influenza antiviral treatments for patients at high risk of severe and life-threatening disease

MG Ison, MD de Jong, KJ Gilligan… – Journal of Infectious …, 2010 – jid.oxfordjournals.org
 of morbidity and mortality than that found in recipients of autologous stem cells [18], and  For
example, one study of hematopoietic stem cell transplantation (HSCT) recipients found that most 
In hospitalized H5N1-infected patients in Vietnam and Indonesia, levels of viral RNA in 

Cross-linking of plant cell walls with dehydrated fructose by smoke-heat treatment

T Hayashi, YW Park, A Isogai, T Nomura – Journal of wood science, 2008 – Springer
 the kiln-drying method.14 Huge amounts of plant cell wall material are wasted worldwide, and
the cell walls are  Because no use has been devised for the oil palm stem waste, a huge amount
of waste (about 8.5 million carbon tons per year in Malaysia and Indonesia) is either 

[HTML] Prospect of induced pluripotent stem cell Genetic repair to cure genetic diseases

J Adiwinata Pawitan - Stem cells international, 2012 – hindawi.com
 Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
C. Chapon, WA Jones, and KK Bhakoo, “Homing of stem cells to sites  injury after intracerebral
and intravenous administration: a longitudinal imaging study,” Stem Cell Research and 

[HTML] Myeloid antigen expression in childhood acute lymphoblastic leukemia and its relevance for clinical outcome in Indonesian ALL-2006 Protocol

E Supriyadi, AJP Veerman, I Purwanto, J Cloos - Journal of oncology, 2012 – hindawi.com
 obvious in situation with lower EFS and LFS, which is the case in Indonesia In summary, myeloid
antigen expression is common and occurs in 25% of Indonesian children with  Singer, JW Adamson,
et al., “Acute nonlymphocytic leukemia: heterogeneity of stem cell origin,” Blood 

International Health Law

J Todres, PL Marcogliese – The International Lawyer, 2005 – JSTOR
 confront avian influenza with Thailand, Indonesia, Malaysia, Singapore, and the Philippines each
responsible for coordinating specific measures to address the disease  Stem Cell Research  ducted
on embryonic and adult stem cells will yield treatments capable of curing serious 

Simple lipoaspirate washing using a coffee filter

JA Pawitan – Asian Biomed, 2013 – abm.digitaljournals.org
 A preliminary study was reported as an oral presentation at the Scientific Meeting of the Indonesian
Anatomist Association, which took place in Denpasar, Bali, Indonesia, October 12–13, 2012.
The authors have no conflict of interest to report.  Stem Cells. 2006; 24: 376-85.

Methotrexate treatment for type 1 (reversal) leprosy reactions

G Biosca, S Casallo… – Clinical Infectious …, 2007 – cid.oxfordjournals.org
 cases have been concentrated in only 6 countries: India, Brazil, Burma, Indonesia, Madagascar,
and  Type 1 leprosy reactions (ie, reversal reactions) indicate a change in cell-mediated immunity 
The treatment of choice is corticosteroid therapy (prednisolone, 40–60 mg per day 

[PDF] Spontaneous bone regeneration after mandible resection in a case of ameloblastoma—a case report

D Coen Pramono – Ann Acad Med Singapore, 2004 – annals.edu.sg
 Prof. Dr. Moestopo 47, Surabaya, Indonesia Classically, they are considered to undergo
differentiation from a common pool of stem or osteoprogenitor cells located perivascularly in  This
model entails the division of a stem cell to yield 2 progenies, one of which remains as a 

Has Oseltamivir been shown to be Effective for Treatment of H5N1 Influenza?

RB Couch, BR Davis – Journal of Infectious Diseases, 2010 – jid.oxfordjournals.org
 on terminal bronchioles and lung alveolar cells, and not on the epithelial cells of the  These results
are similar to those reported earlier for Indonesia and Vietnam but complemented those  150 mg
twice daily) and a longer duration (7–10 days) or parenteral therapy with peramivir 

Antibodies to Plasmodium falciparum and Plasmodium vivax merozoite surface protein 5 in Indonesia: species-specific and cross-reactive responses

T Woodberry, G Minigo, KA Piera… – Journal of Infectious …, 2008 – jid.oxfordjournals.org
 trials of chloroquine and sulfadoxinepyrimethamine therapy or artemisinin combination therapy
(ACT) after  of Health Research and Development, Ministry of Health, Jakarta, Indonesia; the
Menzies  E. coli host cell protein content was determined using an immunoenzymometric 

Cytotoxic and nitric oxide inhibitory activities of methanol extracts of Garcinia species

ML Jabit, FS Wahyuni, R Khalid, DA Israf… – Pharmaceutical …, 2009 – informahealthcare.com
 of the Institute of Bioscience, Universiti Putra Malaysia, and Rusdi Tamin of Andalas University,
West Sumatra, Indonesia About 100 g each of the sample (leaf, stem, bark and fruit) was ground
to  The cell concentrations were set at 3,000, 4,000, and 2,500 cells/well, respectively 

The relationship between periodontal diseases and diabetes: an overview

WA Soskolne, A Klinger – Annals of Periodontology, 2001 – Am Acad Periodontology
 (2013) Stem cells, tissue engineering and periodontal regeneration.  (2011) Periodontitis
Prevalence and Severity in Indonesians With Type 2 Diabetes.  Cell Biochemistry and
Function 23:5, 333. TO Georgiou, RI Marshall and PM Bartold. 

Cytotoxic therapy for severe avian influenza A (H5N1) infection

JI Henter, CB Chow, CW Leung, YL Lau – The Lancet, 2006 – Elsevier
 and Vietnam, whereas the viruses isolated in mainland China and Indonesia generally still  on
corticosteroids, etoposide, cyclosporine A, and intrathecal methotrexate, followed by stem cell
transplantation for  is important for the initiation of apoptosis in target cells, and later in 

[PDF] Reactivation of hepatitis B virus associated with chemotherapy and immunosuppressive agent

I Wijaya, I Hasan – Acta Med Indones, 2013 – inaactamedica.org
 Acta Medica Indonesiana – The Indonesian Journal of Internal Medicine  to and continue to at
least 12 week after chemotherapy.26 Perhimpunan Peneliti Hepatologi Indonesia (PPHI) 2006 
Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus 

[PDF] New research developments increase therapeutic options for thyroid cancer and bone pain palliation

JE Williams – Journal of Nuclear Medicine, 1997 – Soc Nuclear Med
 a material which is so specific and so lethal to cancer cells,―says  are located in Bombay and
New Delhi, India; Ljubljana,Slovenia;Bandung,Indonesia;andSouthAmerica.  rapidexcretionfromthe
body, which might allow greater success with peripheral blood stem cell support of 

Gonadal malignancy in 13 consecutive collected patients with disorders of sex development (DSD) from Semarang (Indonesia)

AZ Juniarto, BA Setyawati, IP Miranti… – Journal of clinical …, 2013 – jcp.bmj.com
 Indonesian DSD patients with ambiguous genitalia or any anatomical abnormality of external
or internal  4 (OCT3/4), Testis-specific Y-encoded protein 1 (TSPY), VASA, stem cell factor (SCF 
were done at the departments of pathology at Diponegoro University, Indonesia and at 

Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-γ receptor 1 deficiency

DC Vinh, F Masannat, RB Dzioba… – Clinical Infectious …, 2009 – cid.oxfordjournals.org
 lower lobe mass with mediastinal and hilar lymphadenopathy compromising the main stem bronchi
and  leading to over-accumulation of mutant IFN-γR1 on the cell surface, which  in IL-12/IFN-gamma
pathway genes with susceptibility to pulmonary tuberculosis in Indonesia

Mass treatment of treponemal diseases, with particular reference to syphilis and yaws

T Guthe, FW Reynolds, P Krag, RR Willcox – British medical journal, 1953 – ncbi.nlm.nih.gov
 A portion of the synovial mem- brane of the left ankle shows infiltration by leukaemic stem cells
an ankle-joint looked normal at necropsy, but was found on histological examination to be
infiltrated by immature leukaemic cells.No evidence  2,270,051 2,270,051 Indonesia (yaws 

Treatment perspectives for the lysosomal storage diseases

GA Grabowski – 2008 – informahealthcare.com
 greatest number of LSD patients should be in China, India and the Indonesian Regions.  Currently,
we have little to offer these patients, except stem cell transplantation in a few  1. Schematic of the
lysosomal enzyme synthesis and targeting systems in mammalian cells (continued 

The hematopoietic stem cell transplantation in Indonesia: an unsolved dilemma

H Hariman – Bone marrow transplantation, 2008 – nature.com
 in the government hospitals in Singapore or Malaysia after having the initial treatment done in
Indonesia hospitals in neighbouring countries becomes more important when they use the PBSC
as source of stem cells Post-transplant problems faced by Indonesian hematologists. 

Expression of human α (1, 3) fucosyltransferase antisense sequences inhibits selectin-mediated adhesion and liver metastasis of colon carcinoma cells

BW Weston, KM Hiller, JP Mayben, GA Manousos… – Cancer research, 1999 – AACR
 In this report, we will show that this variant cell line expresses increased levels of  to examine the
putative role of FUT genes in the metastasis of colon carcinoma cells the function of human
fucosyltransferases and to provide target validation for potential molecular therapy

Scientometric Analysis of Stem cell Research: A comparative study of India and other countries

R Karpagam, S Gopalakrishnan, BR Babu… – COLLNET Journal of …, 2012 – Taylor & Francis
 The members of SNAP are Australia, China, India, Indonesia, Japan, Taiwan, Thailand, Singapore 
focus on the holding of workshops and training programs on stem cell research and  tions,
commercialisation issues and best practices for GMP facilities for cell processing and 

[BUKU] Adipose Stem Cells and Regenerative Medicine

YG Illouz, A Sterodimas – 2011 – Springer
 life sci- entists, and physicians from Brazil, Canada, France, Germany, Greece, Indonesia, Israel,
Italy  Also included are chap- ters on adipose stem cells as therapeutic delivery tools for  to the
safety and ethics consider- ations for developing adipose stem cell-based therapies
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[HTML] The treatment of neurodegenerative disorders using umbilical cord blood and menstrual blood-derived stem cells

PR SanbergDJ Eve, AE Willing… - Cell …, 2011 – cognizantcommunication.com
 International, Inc., Saneron is committed to providing readily available, noncontroversial stem
cells for cellular  relating to our platform technology of umbilical cord blood and Sertoli cellsCell
PRAXIS Bioengenharia is a platform corporation dedicated to translating research into 

Trends of hematopoietic stem cell transplantation in the third millennium

A Gratwohl, H Baldomero – Current opinion in hematology, 2009 – journals.lww.com
 Use of HSCT is under discussion for nonhematopoietic indications, as is the use of
nonhematopoietic stem cells for organ repair.  This will be of increasing importance, since stem
cell therapy has become a treatment vision for many patients with diseases that are not yet 

Application of a modified method for stem cell isolation from lipoaspirates in a basic lab

CT Sardjono, M Setiawan, F Frisca, V Saputra… – … Journal of Indonesia, 2009 – mji.ui.ac.id
 This report clearly has shown the urge for stem cell research to be conducted in Indonesia as
soon as possible  This study has demonstrated that it is possible to isolate mesenchymal stem
cells from the lipoaspirate using a  Lipoaspirate is truly rich with Mesenchymal Stem cell

Treatment of acute lymphoblastic leukemia

CH Pui, WE Evans – New England Journal of Medicine, 2006 – Mass Medical Soc
 Allogeneic Hematopoietic Stem-Cell Transplantation.  prevention of traumatic lumbar punctures,
especially at diagnosis, when most patients have abundant circulating leukemia cells.95,97  to
imatinib.99 Imatinib may also benefit a subgroup of patients who have T-cell ALL with 

[PDF] Adult bone marrow stem cells in cartilage therapy

AM Lubis, VK Lubis – Acta Medica Indonesiana, 2012 – inaactamedica.org
Page 1. REVIEW ARTICLE 62 Acta Medica Indonesiana – The Indonesian Journal of Internal
Medicine  4, Jakarta, Indonesia. Correspondence mail: andri_lubis@yahoo.com. 2 Innogene
Kalbiotech, Pte.Ltd., Jakarta, Indonesia Stem Cells. 2007;25:2964-71. 32. 

Screening of Indonesian medicinal plants for inhibitor activity on nitric oxide production of RAW264. 7cells and antioxidant activity

EM Choi, JK Hwang – Fitoterapia, 2005 – Elsevier
 In this study, we investigated several medicinal plant extracts traditionally and commonly used
in Indonesia, and focused our  Effects of Indonesian plants methanol extracts on NO production
and viability of RAW264.7 cells Alstonia scholaris, Stem bark, 13.0, 50, −9.4±9.4, 71.5±0.5 

Methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase promoter (TSER) polymorphisms in Indonesian children with and without leukemia

E Giovannetti, DG Ugrasena, E Supriyadi, L Vroling… – Leukemia research, 2008 – Elsevier
 can be treated), it might represent an undertreatment for Indonesian children, who  the required
higher dose of MTX in paediatric patients of Indonesia might be  and thymidylate synthase
genotypes modify oral mucositis severity following hematopoietic stem cell transplantation. 

Quantum dots for cancer diagnosis and therapy: biological and clinical perspectives

H Zhang, D Yee, C Wang – 2008 – Future Medicine
 Recent and future progress on tracking therapeutic stem cells with QDs for treating cardiovascular
diseases  can measure levels of molecular targets quantitatively on the tumor cell surface will  Finally,
targeted therapy against an overexpressed molecular target will be used on 

[HTML] Development of Histocompatible Primate‐Induced Pluripotent Stem Cells for Neural Transplantation

M Deleidi, G Hargus, P Hallett, T Osborn… - Stem Cells, 2011 – Wiley Online Library
 with N 2 -A (Stem Cell Technologies, Vancouver, BC, Canada, www.stemcell.com  and MF
66-02) (Supporting Information Table 1). Dermal fibroblasts from an Indonesian CM (MF  under
Good Manufacturing Practice, would be of great value to evaluate stem cell-based therapies 

Atovaquone/proguanil therapy for Plasmodium falciparum and Plasmodium vivax malaria inIndonesians who lack clinical immunity

MD Lacy, JD Maguire, MJ Barcus… – Clinical Infectious …, 2002 – cid.oxfordjournals.org
 Diseases, National Institute of Health Research and Development, Ministry of Health, Republic
of Indonesia, Jakarta, Indonesia Atovaquone/proguanil provided safe, well-tolerated, and effective
therapy for uncomplicated malaria in nonimmune Indonesians
 

HTML] Prospect of cell therapy for Parkinson’s disease

JA Pawitan – Anatomy & cell biology, 2011 – synapse.koreamed.org
 Salemba 6, Jakarta 10430, Indonesia Tables. Table 1 Various studies on cell therapy in animal
models and patients eNCSCs, epidermal neural crest stem cells; BM-SCs, bone marrow stem
cells; hESCs, human embryonic stem cells; RPE, retinal pigment epithelium. 

Pigmentation PAX‐ways: the role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease

JD Kubic, KP Young, RS Plummer… – Pigment cell & …, 2008 – Wiley Online Library
 syndromes resulting from either too much or too little Pax3 function. Due to its key
task in melanocyte stem cells and tumors, the Pax3 pathway may provide an ideal
target for either stem cell or cancer therapies. Introduction. 

Effects of implantation of bone marrow mesenchymal stem cells, disc distraction and combinedtherapy on reversing degeneration of the intervertebral disc

HT Hee, HD Ismail, CT Lim… – Journal of Bone & …, 2010 – bjj.boneandjoint.org.uk
 Siregar, and her staff in Eijkman Institute for Molecular Biology, Jakarta, Indonesia: L. Yunaini,
Nur Ita M, and M. Rusdi H, for  Differentiation of mesenchymal stem cells transplanted to a rabbit
degenerative disc model: potential and limitations for stem cell therapy in disc 

Novel agents and strategies for treatment of< i> p53</i>-defective chronic lymphocytic leukemia

MR Grever, DM Lucas, AJ Johnson, JC Byrd – Best Practice & Research …, 2007 – Elsevier
 Allogeneic stem-cell transplant likely represents the only curative therapy for CLL.  pentostatin,
and/or alemtuzumab – has resulted in the ability to engraft allogeneic cells from a related  has
increased the number of CLL patients eligible for allogeneic immune therapy to patients 

A trial of the effect of micronutrient supplementation on treatment outcome, T cell counts, morbidity, and mortality in adults with pulmonary tuberculosis

E Villamor, F Mugusi, W Urassa… – Journal of Infectious …, 2008 – jid.oxfordjournals.org
 One trial in Indonesia suggested a potential beneficial effect of vitamin A and zinc on early sputum
smear conversion  Effect of micronutrient supplementation on T cell counts (cells/mm 3 ) and viral
load (copies/mm 3 ).  In a study of 80 Indonesians with pulmonary TB, Karyadi et al 

… , placebo-controlled trial of atovaquone/proguanil for the prevention of Plasmodium falciparum or Plasmodium vivax malaria among migrants to Papua, Indonesia

J Ling, JK Baird, DJ Fryauff, P Sismadi… – Clinical infectious …, 2002 – cid.oxfordjournals.org
 double-blinded trial of atovaquone/proguanil for malaria prophylaxis in Indonesians who did
not  village, a mixture of people from Java, other islands of Indonesia, or the  chloroquine,
pyrimethamine/sulfadoxine, or quinine therapy, consistent with the Indonesian national malaria 

[HTML] Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents

E Meiyanto, A Hermawan… – Asian Pacific Journal of …, 2012 – koreascience.or.kr
 The Anti-Tumor Effect of Doxorubicin on Hela Cervical Cancer Cells Through Cytotoxic Activity
and Apoptosis Induction, Indonesian J Cancer  (In Indonesia).  and YB-1 Expression Plays a Role
In Increased Heterogeneity of Breast Cancer Cells: Correlations with Cell Fusion and 

Encephalomyelitis Due to Infection with Herpesvirus simiae (Herpes B Virus) A Report of Two Fatal, Laboratory-Acquired Cases

K Hummeler, WL Davidson, W Henle… – … England Journal of …, 1959 – Mass Medical Soc
 Basic principles for stem cell culture. In: Progenitor and stem cell technologies and therapies
6. John R Masters, Glyn N Stacey. (2007) Changing medium and passaging cell lines.  (2005)
Prevalence of enzootic simian viruses among urban performance monkeys in Indonesia

Indonesian tea mistletoe (Scurrula oortiana) stem extract increases tumour cell sensitivity to tumour necrosis factor alpha (TNFα)

R Murwani – Phytotherapy Research, 2003 – Wiley Online Library
 The stem extract showed a greater increase than the leaf extract, increasing the sensitivity more 
Indonesian tea mistletoe (‘benalu teh’) (Family Loranthaceae) is a parasitic plant that grows on 
In Indonesia, especially in Java, its potency as an (indigenous) anti-tumour agent has 

Stem cell stratagems in alternative medicine

D Sipp - Regenerative medicine, 2011 – Future Medicine
 121 . BRCO Stem Cell Indonesia http://xenostemcell-indonesia.com. 122 .  123 . Stem Cell
Biomedics www.stemcell-biomedics.com. 124 . Fetal Stem Cell International medical advisory
panel http://www.fetal-cells.com/index.php?Content=advisory. 125 . 

In the Literature

WJ Burman, S Goldberg, JL Johnson – tuberculosis, 2006 – cid.oxfordjournals.org
 The authors caution, however, against the reinstitution of chloroquine as standard therapy for
malaria in Malawi, because this country is surrounded by other countries in  Human H5N1 Infection
In Indonesia And Turkey.  Three Indonesian clusters of H5N1 virus infection in 2005. 

[BUKU] Advanced therapy in cardiac surgery

KL Franco, ED Verrier – 2003 – books.google.com
 com Singapore, Malaysia, Thailand, Philippines, Indonesia, Vietnam, Pacific Rim, Korea Elsevier
Science Asia  PhD, Barbara Cattadori, MD, MS, Alain Carpentier, MD, PhD 44 Cell Therapy for
Myocardial  E. Beschorner, MD 60 Role of Gene Therapy and Stem Cells in Cardiac 

[PDF] Isolation and cultivation of mesenchymal stem cells from iliac crest bone marrow for further cartilage defect management

AM Lubis, L Sandhow, VK Lubis, A Noor… – Acta Med …, 2011 – inaactamedica.org
 study has been approved by Ethical Committee of the Faculty of Medicine University of
Indonesia/Cipto Mangunkusumo  E, McGonagle D, Scutt A. Age-related changes in human bone
marrow-derived mesenchymal stem cells: consequences for cell therapies

C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-basedtherapy personalisation

E De Mattia, G Toffoli – European Journal of Cancer, 2009 – Elsevier
 These data could suggest that the C677T polymorphism differentially modulates the sensitivity
of cancer cells to MTX, depending upon the specific cell type. 64 In view of the importance of
MTX in the therapy of adult and paediatric lymphoid malignancies, particularly during 

Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen)

AR Han, JA Kim, DD Lantvit, LBS Kardono… – Journal of natural …, 2009 – ACS Publications
 Research Center for Biology, Indonesian Institute of Science  stem bark of G. mangostana (400
g) was collected at Pangradin village, Jasinga, West Java, Indonesia, in August  Extraction and
Isolation The dried stem bark of G. mangostana (400 g) was extracted with MeOH (3 × 1 

Primaquine therapy for malaria

JK Baird, SL Hoffman – Clinical infectious diseases, 2004 – cid.oxfordjournals.org
 Vivax malaria is especially common in India, Indochina, and the Philippine, Indonesian and New 
ovale malaria occurs only in West Africa, The Philippines, Eastern Indonesia, and Papua  when
given concurrently with blood schizonticides [40–42] (table 2). Indonesians who took 

Platelet rich plasma in xeno-free stem cell culture: the impact of platelet count and processing method

J Adiwinata Pawitan – Current stem cell research & therapy, 2012 – ingentaconnect.com
 This study is funded by the grant from the Directorate of Research and Community Service of
Universitas Indonesia 2012, Contract no.1594/H2.R12/HKP.05.00  Internalized antigens must
be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene 

Dissecting the molecular pathways of (testicular) germ cell tumour pathogenesis; from initiation totreatment‐resistance

LHJ Looijenga, AJM Gillis, H Stoop… – … journal of andrology, 2011 – Wiley Online Library
 or differentiation, resulting in loss of characteristics of embryonic germ – and stem cells, or a  that
in spite of this cancer being rare in the general Indonesian population, in  Interestingly, in
Drosophila communication between soma and germ cell initiating germ line sexual identity 

[BUKU] Essential haematology

V Hoffbrand, P Moss – 2011 – books.google.com
 1996, 1997, 1998, 1999, 2000 Fourth edition 2001 German 2002 Indonesian 2005 Korean  62
■VitaminB 12 deficiency 63 ■ Folate deficiency 64 ■ Tissue-specific stem cells 5 ■
Theregulation  factors 6 ■ Growth factor receptors and signal transduction 8 ■ The cell cycle 

Results of a prospective study for the treatment of unilateral retinoblastoma

GL Chantada, AC Fandiño, MR Guitter… – Pediatric blood & …, 2010 – Wiley Online Library
 Choroidal invasion was categorized as full when tumor cells invaded the choroid >50% of it  of
treatment was significantly associated to poor prognosis in an Indonesian series 27  could be
rescued with chemotherapy followed by intensification and autologous stem cell rescue. 

[PDF] Immunophenotypic patterns of childhood acute leukemias in Indonesia

YM Purwanto, S Gunawan… – Asian Pacific Journal …, 2011 – apocpcontrol.com
 until July 2010 were received from Pediatric Cancer Units (PCU) of four Indonesian teaching
hospitals  Expression of the stem cell factor receptor C-KIT (CD117) in acute leukemias.  Purwanto
I, et al (2011) Incidence of childhood leukemia in Yogyakarta, Indonesia, 1998 – 2009. 

Updates on current advances in gene therapy.

J Tani, JT Sufian – West Indian Medical Journal, 2011 – search.ebscohost.com
 Cipto Mangunkusumo Hospital, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
and 3Peking  59) in order to confer specific protection against HIV infection to these cells Both
clinical T cell and haemato- poietic stem cell gene transfer trials have demonstrated 

Current status of hematopoietic stem cell transplantation in Taiwan

PM Chen, LT Hsiao, MH Chen, PMS Chang… – Bone marrow …, 2008 – nature.com
 Transfusion of donor peripheral blood buffy coat cells as effective treatment for relapsed acute
leukemia after transplantation of allogeneic bone marrow or peripheral blood stem cells from
the  The hematopoietic stem cell transplantation in Indonesia: an unsolved 

[HTML] Transgenic animals: Their benefits to human welfare

ET Margawati – American Institute for Biological Sciences, 2003 – actionbioscience.org
 isolation of totipotent stem cells (stem cells that can develop into any type of specialized cell) from
embryos; the desired gene is inserted into these cells D and is now working at the Research Centre
for Biotechnology, the Indonesian Institute of Sciences , Indonesia

Smenospongine, a spongean sesquiterpene aminoquinone, induces erythroid differentiation in K562cells

S Aoki, D Kong, K Matsui, M Kobayashi – Anti-cancer drugs, 2004 – journals.lww.com
 leukemia (CML) arises from chromosomal abnormality in a pluripotent hematopoietic stem cell
further isolated smenospongine, a sesquiterpene aminoquinone, from an Indonesian marine
sponge.  from the marine sponge Dactylospongia elegans (collected in Indonesia in 2001 

… association of interleukin-6 and lipopolysaccharide-binding protein with severity of adverse reactions after diethylcarbamazine treatment of microfilaremic patients

M Haarbrink, GK Abadi, WA Buurman… – Journal of Infectious …, 2000 – jid.oxfordjournals.org
 the inflammatory processes via both the monocyte/macrophage or the T cell—stimulation route. 
We gratefully acknowledge the assistance in Indonesia of Abdul Jalil, Abdul Rashid, Sidra  and
blood withdrawal, in accordance with the guidelines of the Indonesian Department of 

Stem cells and regenerative medicine on the Asian horizon: an economic, industry and social perspective

D Sipp - Regenerative medicine, 2009 – Future Medicine
 in which stem cell research is minimal, including Thailand, the Philippines, Indonesia and Malaysia 
Theravitae, a company based in Bangkok, Thailand, offers autologous stem cell therapies for
congestive heart failure and peripheral vascular disease, sending the cells to Israel 

[PDF] Umbilical Cord Blood: the Future of Stem Cell Research?

E Lloyd – National Geographic News, 2006 – cordlife.com
 CORDLIFE SINGAPORE BIOCELL AUSTRALIA CORDLIFE HONG KONG CORDLIFE INDONESIA
CORDLIFE PHILIPPINES  cell technology will come from and what kinds of stem cells will be 
President George W. Bush signed into law the Stem Cell Therapeutic and Research 

The pathogenesis of rheumatoid arthritis

IB McInnes, G Schett – New England Journal of Medicine, 2011 – Mass Medical Soc
 into adipocytes, chondrocytes, and osteoblasts, can be detected in the synovium.80,81 However,
the biologic characteristics of synovial mesenchymal stem cells, their relationship  Cell-cell
interactions in synovitis: interactions between T lymphocytes and synovial cells

Emerging chloroquine-resistant Plasmodium vivax (Benign Tertian) malaria: the need for alternative drug treatment

JM Vinetz - Clinical Infectious Diseases, 2006 – cid.oxfordjournals.org
 latent liver forms (hypnozoites), necessitating an additional course of primaquine therapy (after
assessing  chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria
in Papua, Indonesia Malaria in a cohort of Javanese migrants to Indonesian Papua. 

Ethnic differences in the frequency of subtypes of childhood acute lymphoblastic leukemia: results of the Malaysia-Singapore Leukemia Study Group

H Ariffin, SP Chen, CS Kwok, TC Quah… – Journal of pediatric …, 2007 – journals.lww.com
 from Malaysia and Singapore (mostly Malay and Chinese), and also Indonesia, Brunei, and  Total
RNA was extracted from leukemic cells by Trizol reagent (Invitrogen, Carlsbad, CA  Leukemic
cell lines positive for the respective chromosomal alterations 15 were included, while 

[PDF] … granulocyte colony stimulating factor and erythropoetin based-stem cell therapy using intracoronary infusion of peripheral blood stem cells in patients with …

T Santoso, C Irawan, I Alwi, A Aziz, A Kosasih… – Acta Med …, 2011 – inaactamedica.org
 Medistra Hospital, Jakarta, Indonesia. Correspondence mail to: tsantoso@cbn.net.
id  G-CSF-based stem cell therapy has been proposed as a practical and non-invasive
alternative to stem cell therapy using bone marrow stem cells

Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature

BJ Currie, DA Fisher, DM Howard… – Clinical Infectious …, 2000 – cid.oxfordjournals.org
 Burma (Myanmar) and was recognized in patients in Vietnam and Indonesia decades before 
The clinical presentations of brain stem encephalitis with peripheral motor weakness, including
acute  when there is coinfection with HIV, suggesting that CD4 cell-mediated defense 

Mefloquine is highly efficacious against chloroquine-resistant Plasmodium vivax malaria and Plasmodium falciparum malaria in Papua, Indonesia

JD Maguire, H Marwoto, TL Richie… – Clinical infectious …, 2006 – cid.oxfordjournals.org
 on clearance of parasitemia and clinical cure in the face of ineffective chloroquine therapy during
the intervening period, because mefloquine has not been available in Indonesia and, therefore,
is not a factor in the development of selective resistance in Indonesian Papua. 

Influenza surveillance in Indonesia: 1999–2003

CG Beckett, H Kosasih, C Ma’roef… – Clinical infectious …, 2004 – cid.oxfordjournals.org
 All participants were Indonesian and residents of each sentinel city of surveillance.  mnRT-PCR)
for detection of influenza viruses, compared with virus isolation using cell culture  In particular,
because Indonesia straddles the equator, virological surveillance data could be used to 

Randomized, parallel placebo-controlled trial of primaquine for malaria prophylaxis in Papua,Indonesia

JK Baird, MD Lacy, H Basri, MJ Barcus… – Clinical infectious …, 2001 – cid.oxfordjournals.org
 Blood cell counts were analyzed (Becton Dickinson QBCII Plus Analyzer system and reagents),
as  gratitude to many officers of the Ministry of Health, Republic of Indonesia, for their  This study
was reviewed and approved by American and Indonesian committees for the ethical 

Stem cell transplantation programme at Singapore General Hospital

MBC Koh, YT Goh, PHC Tan, LP Koh… – Bone marrow …, 2008 – nature.com
 Exp Haem 2005; 33: 671–681. Suck G. Novel approaches using natural killer cells in cancer therapy
REVIEWS. The hematopoietic stem cell transplantation in Indonesia: an unsolved dilemma. Bone
Marrow Transplantation Review. See all 10 matches for Reviews. 

Aplasia and leukaemia following chloroquine therapy.

N Nagaratnam, AD Chetiyawardana… – Postgraduate medical …, 1978 – pmj.bmj.com
 2 showing increase of fat spaces with islets of cells (HE, x 100); (b) same, with islets of cells and
fat  In the other, there is a strong suggestion of a stem cell lesion.  Third Meeting of the Inter- national
Society of Haematology, Asian-Pacific Division, June 1975,Jakarta, Indonesia

Antiproliferative effect of the methanol extract of Piper crocatum ruiz & pav leaves on human breast (T47D) cells in-vitro

BD Wicaksono, YA Handoko, ET Arung… – Tropical Journal of …, 2009 – ajol.info
 is traditionally used by Indonesians for treating various diseases, including breast cancer9.  T47D
cells were obtained from the Indonesian Institute of Sciences Research Centre for Chemistry,
Natural Products, Food and Pharmaceuticals Division, Bandung, Indonesia

Estrogen replacement therapy induces telomerase RNA expression in the macaque endometrium

JD Vidal, TC Register, M Gupta, JM Cline – Fertility and sterility, 2002 – Elsevier
 study were adult female cynomolgus macaques (Macaca fascicularis) imported from Indonesia
as subjects  expression, which is consistent with the histopathologic observations of stromal cell
hyperplasia and  layer is shed at menses and is repopulated from stem cells within the 
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The development of stem therapy in Indonesia
Stem Cell Therapy Could Prevent Various Diseases
Qalbinur Nawawi – Okezone
THURSDAY , NOVEMBER 7 2013 14:57 pm
 
The discussion ( Photo : qalbi / Okezone )
THROUGH Dr . Boenjamin Setiawan Distinguished Lecture Series 2013 , Dr . Boenjamin Setiawan, PhD , Chairman of the Scientific Advisory Board of Stem Cell and Cancer Institute , to educate the public about the research and development of health technology . One of them is that stem cell therapy , the results of the latest medical technology and treatment is believed to answer the needs of Indonesia in the future .

 
Stem cells or stem cell is a cell that can reproduce itself and has the ability to differentiate into many cell . Because of this ability , the potential of stem cells to regenerate damaged cells or dysfunction in many diseases and potential to cure many incurable diseases .
 
” Stem cells are the future of medicine and can cope with various diseases .
 In our bodies there are many cells , such as bone marrow and fat cells in our body .
Cells in our own bodies there are 100 trillion cells , and every day there will be a lot of dead and all.
 All it takes is regenerated and the efforts of the solutions come from stem cell therapy , ” said Dr. . Boenjamin Setiawan, PhD , Chairman of the Scientific Advisory Board of Stem Cell and Cancer Institute in the event themed Increasing Quality Life Through Cell Therapy at the University Tarumanagara Main Building , Auditorium Room 3rd Floor , West Jakarta , Thursday ( 07/11/2013 )
 

” Our body is like a car , which is often used when the inevitable damage .
 And it can be fixed with stem cell therapy through the ‘ five R ‘ . First , replacing damaged cells or to repair and replace , then regenerated by stem cell therapy , and the fourth R rehabilitated . Anyway , all the damaged cells enhanced , then finally rejuvenated , “he continued .
 
The biggest benefit of stem cell therapy is very diverse , can make the skin taut and youthful look , then also can cure incurable diseases .
 
” So far , stem cell therapy is still small . RSCM itself which is the reference point of all disease , had stem cell therapy to cure four diseases . Firstly , osteoarthritis handled dr . Andri Lubis , Sp.OT , heart attack or heart , burns , and fractures that do not want to connect – connect , ” he explained .
 
Not merely that, this stem cell therapy can cure degenerative diseases , such as heart failure , cartilage injury , stroke , diabetes , and kidney failure .

 However, to be able to get the formula of the treatment of degenerative it should continue to be extracted by the related parties , primarily academics and practitioners , as well as the government .
The goal is that the more types of diseases that can be cured by this stem cell therapy .
Where indirect already advancing research and development of health technology in Indonesia .
 
” The existence of this educational program and sharing so that existing lecturers in medical school ikutresearch , not just teaching in the classroom .
It was because of the many benefits that can be cured of this cell therapy . I wish health and health technology Indonesian move on and do not be retarded . Do not want to be followers . And to achieve that , the teachers can not only in the classroom alone . They must participate researching , ” he explained .
 
Meanwhile , the education program itself runs from 6-8 November 2013 in Jakarta, which is housed in several large campuses in Jakarta , namely the University of Atma Jaya , Tarumanegara University , University of Indonesia and the peak of the event will be held at the Four Seasons on 9 November 2013 .
( tty )
Dr. . Boenjamin Setiawan, PhD
 
dr . Boenjamin Setiawan, Ph.D.

This is one example of a figure model of health that have multidimensional mindset . Broad insights to help successful reading opportunities .
Consistency will be the nature of his concern for the world of medical research in Indonesia helped memerbanyak existing business opportunities .
Establish a pharmacological company had indeed ideals of the ancients . His experience in fostering research memerkaya helped perpetuate the success of Kalbe Farma road gait .
He is one of the exemplary model of health . Open minded but firm .
Kalbe Farma is the founding manifesto of a sense of love for the field of pharmacology .
Also, concern for the progress of the development of medical science gets a share of attention in developing the health agenda in Indonesia .
 
Not a bit of research it supports . As well as well as some foundations that receive special attention in the advancement of health .
Here are some of them who built the foundation , Foundation for the Development of Human Resources in 1970 and the Foundation for Development of Creativity in 1985 .
Pun , who cultivated many pharmacological companies supported by the results of scientific research in its development process .
He is a multi – dimensionil doctor and has a soul of steel -minded entrepreneurs

Perkembangan stem terapi di Indonesia

Terapi

 Stem Cell 

Bisa Cegah Beragam Penyakit

Qalbinur Nawawi – Okezone

 

 

KAMIS, 7 NOVEMBER 2013 14:57 wib

Acara diskusi (Foto: Qalbi/Okezone)

MELALUI

 Dr. Boenjamin Setiawan Distinguished Lecture Series 2013, Dr. Boenjamin Setiawan PhD, Chairman of Scientific Advisory Board Stem Cell and Cancer Institute, memberikan edukasi kepada masyarakat mengenai perkembangan riset dan teknologi kesehatan. Salah satunya ialah terapi stem cell

, hasil teknologi kesehatan terbaru dan diyakini bisa menjawab kebutuhan pengobatan Indonesia di masa depan.

 

 

 

 

Stem cell atau sel punca merupakan sel yang bisa memperbanyak dirinya dan mempunyai kemampuan untuk berdiferensiasi menjadi banyak sel. Karena kemampuannya ini, stem cell berpotensi untuk meregenerasi sel yang rusak atau disfungsi dalam berbagai penyakit dan potensial untuk menyembuhkan berbagai penyakit yang sulit disembuhkan.
 
Stem cell

 merupakan pengobatan masa depan dan bisa mengatasi beragam penyakit.

Dalam tubuh kita terdapat banyak sel, seperti di sumsum tulang belakang dan sel lemak dalam tubuh kita.

Sel dalam tubuh kita sendiri ada 100 triliun sel dan setiap hari akan ada yang mati dan banyak sekali.

Semua itu butuh diregenerasi dan upaya itu jalan keluarnya datang dari terapi 

stem cell,” kata Dr. Boenjamin Setiawan PhD, Chairman of Scientific Advisory Board Stem Cell and Cancer Institute dalam acara bertema Increasing Quality Life Through Cell Therapy

 di Gedung Utama Universitas Tarumanagara, Ruang Auditorium Lantai 3, Jakarta Barat, Kamis (7/11/2013)
 

 

 

 

“Badan kita itu ibarat mobil, di mana saat sering dipakai pasti terjadi kerusakan.

Dan itu bisa diperbaiki dengan terapi 

stem cell melalui ‘lima R’. Pertama, sel yang rusak diganti atau di-repair dan replace, kemudian diregenerasi melalui terapi stem cell, dan R keempat direhabilitasi. Pokoknya, semua sel yang rusak disempurnakan, kemudian akhirnya diremajakan,” sambungnya.
 
Manfaat terbesar terapi 
stem cell ini sangat beragam, bisa membuat kulit kencang dan tampak awet muda, kemudian juga bisa menyembuhkan penyakit yang sulit disembuhkan.
 
“Sejauh ini, terapi 
stem cell masih sedikit. RSCM sendiri yang merupakan tempat rujukan semua penyakit, sudah terapi stem cell

 untuk penyembuhan empat penyakit. Pertama, osteoartritis yang ditangani dr. Andri Lubis, Sp.OT, serangan jantung atau jantung, luka bakar, dan patah tulang yang tidak mau menyambung-nyambung,” jelasnya.
 

 

Tak sebatas itu, terapi stem cell ini bisa menyembuhkan penyakit degeneratif, seperti gagal jantung, cedera tulang rawan, stroke, diabetes, dan gagal ginjal

.

 

 

Kendati demikian, untuk bisa mendapat formula dari pengobatan degeneratif itu  harus terus digali oleh pihak terkait, utamanya akademisi dan praktisi, serta pemerintah.

 

Tujuannya agar makin banyak jenis penyakit yang bisa disembuhkan oleh terapi 

stem cell ini.

 

Di mana secara tak langsung sudah memajukan perkembangan riset dan teknologi kesehatan di Indonesia.
 
“Adanya program edukasi dan 

sharing ini agar para dosen yang ada pada fakultas kedokteran ikutresearch, bukan hanya sekadar mengajar di kelas.

Hal itu karena banyak manfaat yang bisa disembuhkan dari terapi sel ini. Saya ingin teknologi kesehatan dan kesehatan Indonesia maju terus dan jangan terbelakang. Jangan mau jadi 

follower. Dan untuk mencapai hal itu, para dosen tidak bisa hanya dalam kelas saja. Mereka harus ikut meneliti,” jelasnya.
 

Sementara itu, program edukasi ini sendiri berlangsung dari tanggal 6-8 November 2013 di Jakarta yang bertempat di beberapa kampus besar di Jakarta, yaitu Universitas Atmajaya, Universitas Tarumanegara, Universitas Indonesia dan puncak acara akan dilaksanakan di Hotel Four Seasons pada 9 November 2013

.

(tty)

 

Dr. Boenjamin Setiawan PhD

 

 

 

dr. Boenjamin Setiawan Ph.D.

 

I

nilah salah satu contoh figur tokoh kesehatan yang memiliki pola pikir multidimensional. Wawasannya yang luas membantu sukses membaca peluang yang ada.

Konsistensi akan sifat kepeduliannya pada dunia penelitian medis di Indonesia membantu memerbanyak peluang usaha yang ada.

Mendirikan perusahaan farmakologi merupakan sudah memang cita-citanya dari dahulu. Pengalamannya dalam membina memerkaya penelitian-penelitian turut membantu melanggengkan jalan kiprah kesuksesan Kalbe Farma.

Beliau merupakan salah satu tokoh kesehatan yang patut diteladani. Pikirannya terbuka namun tegas.

Berdirinya Kalbe Farma merupakan manifesto dari rasa kecintaannya pada bidang farmakologi.
Pun, kepeduliannya kepada kemajuan perkembangan ilmu kesehatan mendapatkan porsi perhatian dalam agenda mengembangkan kesehatan di Indonesia.

Tidak sedikit penelitian yang didukungnya. Serta pula beberapa yayasan yang mendapatkan perhatian khusus dalam kemajuan bidang kesehatan.

Berikut diantaranya beberapa yayasan yang didirikannya yakni, Yayasan Pengembangan Sumber Daya Manusia pada tahun 1970 dan Yayasan Pengembangan Kreatifitas pada tahun 1985.

Pun, perusahaan farmakologi yang dibinanya banyak didukung oleh hasil-hasil penelitian ilmiah dalam proses pengembangannya.

Beliau merupakan dokter multi-dimensionil serta memiliki jiwa pengusaha yang bermental baja. []s

Kalbe, The Making of No. 1 Pharma

Kalbe , The Making of No . 1 Pharma
Thursday, June 1, 2006
By : Prih Sarnianto
Through the merger , Kalbe Farma burst into the top ranks of pharmaceutical companies terakbarIndonesia . What are the strengths that enable them become the biggest in the ASEAN region ?
This is the grandest marriage in Indonesian business stage . Through the internal merger , PT Kalbe Farma Tbk . as the surviving company overtake Sanbe Farma fluttering over the years at the peak of the largest pharmaceutical companies in the country .
In fact , more than that . With a market capitalization of U.S. $ 2 billion , the company whose shares are listed on the Jakarta Stock Exchange with code KLBF also establish itself in the top ranks of public companies in Southeast Asia .
In terms of sales , Kalbe result of a merger that grossed $ 267.2 million revenueUS , in the Southeast Asian region is second only to Pfizer and GlaxoSmithKline ( GSK ) is indeed the world pharmaceutical industry giant .
Nevertheless, as a group of pharmaceutical business , Kalbe Group is actually always the biggest .
Understandably , under the umbrella of one ‘s business empire , directly or indirectly there are big names , including Toedjoe star ( Extra Joss producers who enter the ranks of Top 10 Pharmaceutical Companies in Indonesia ) , Hexpharm ( the largest generic drug manufacturer in the 5th Indonesia ) , Saka Farma ( ABC Sakatonic remember ? ) , Mighty Biosciences ( producer Prenagen , Diabetasol , and other health foods ) , Kalbe Morinaga ( leading dairy producer ) , Innogene Kalbiotech ( biotechnology -based drug manufacturer in Singapore ) and Kageo Igar Jaya ( packaging ) .
Mergers involving PT Enseval sebagaisuperholding and three companies listed on the JSE – Kalbe Farma , Dankos Laboratories ( DNKS ) , Enseval Son Megatrading ( EPMS ) – as well as forming a company that truly integrated . Horizontally , Kalbe ” new ” offer a product range that is much wider , ranging from various forms of drug and health food supplements and energy drinks through . Vertically, they perform activities from procurement of raw materials , finished product manufacturing , marketing , to sales and distribution.
Consolidation is done , Kalbe officials and analysts predict , will improve the efficiency of business operations . For any procurement , centralized management will make bargaining power increases so that the purchase price of raw materials can be reduced . Inventory will also be more efficient . Similarly , economies of scale production skyrocketed .
On the marketing side , the allocation of funds for the expansion of the market will swell to new markets that can be worked will also be much more extensive and , tail , improve competitiveness . Marketing efforts are cleverly divided by the market from various sides – OTC ( over-the- counter drugs that can be sold freely , without a doctor’s prescription ) , ethical ( prescription drugs ) , hospitals , physician practices , medical specialists , institutions – can be done more focused .
“If the company is not large , do this responsibility , ” said Herman Widjaja . The reason , according to the Kalbe Group Marketing Director , for maintaining that particular row salespeople were required considerable additional cost .
Beyond the issue of efficiency , the merger is done to stop the ” civil war ” that has been happening . Previously , people Kalbe and Dankos , for example , because it knows properly the contents of the stomach , respectively , in each field with fierce jegal . With the merger that made them into one team , aggressiveness on the field will certainly be transferred to outside competitors .
Remarkably , despite civil war , Kalbe and Dankos pramerger can share market area . In product categories flu medicine , for example , Kalbe Procold carrying flags fluttering in Indonesia Region West , from Central Java and Jakarta . Meanwhile , Mixagrip which bears the name of Dankos strong in eastern Indonesia , ranging from East Java to Bali , East Nusa Tenggara and Sulawesi . Not surprisingly , both of these brands so equally large and in the aggregate owns 40 % of the national market .
Separation of the market , according to Herman , was not formally designed . Nevertheless, he said , ” We , right , perform in a focused marketing activity so as not to overflow into all areas . So , the bags are formed . ” Reason behind this ? ” To be ( in marketing efforts ) do not run out of funds . “
In terms of sales , Mixagrip become the market leader with a share of around 30 % so that even surpass Procold lost Ultraflu ( Henson pharma ) and Decolgen ( Medifarma ) .
However , mastering the higher market segments ( mass affluent and middle mass ) , Procold provide higher profit margins than Mixagrip the lower market segments (middle massdan lower mass ) .
The division of the target market segments like this is definitely not a coincidence . In 1974 , when Procold launched , the market for flu drugs lower-middle segment is very crowded . Therefore , Kalbe Procold then positioned on top of the local products that have mastered the lower segment through price competition , but still below the industry champion of foreign pharmaceutical products . For the market segment under greater – in 2005 , mass pasarlower size estimated at U.S. $ 900 million or much larger than the mass middle market ( U.S. $ 400 million ) , mass affluent ( U.S. $ 300 million ) or affluent ( U.S. $ 400 million ) – many years later Kalbe candidate Mixagrip produced Dankos .
Powered bold marketing efforts and painstaking , positioning the tandem paired proven to seize the market in all segments – from the bottom up . Although overall sales Procold ranks only 4th , for the upper – middle segment Kalbe flu drug product is still above Neozep and the like . Thus , in one category only products of this fat , Kalbe has created two major growth engine .
What do they do when conquering the market category of medicinal products arguably typical flu Kalbe . Established in 1966 , since the beginning Boenjamin Setiawan want to put Kalbe as the company that owns differentiation . When taking a pharmacology Ph.D. program at the University of California , Boenjamin who was then a young lecturer at the Faculty of Medicine, University of Indonesia sees growth opportunities not only pharmaceutical company that produces generic drugs in the country .
” Products are made to be unique , different from the existing ones in the market , ” said dr . Boen . ” And , the product must be marketed with a good strategy . “
However , despite a clear vision , not easy to be a business to make it happen . The proof , initial efforts dr . Young Boen with some fellow lecturers FKUI failed .
In 1963 , a new two -year return of the United States , socio- economic condition of Indonesia may not have been too conducive to a business with great ideals . Or maybe , he and his friends are fellow physicians experienced no run business so chaotic results.
Fortunately , Boen not despair though was tempted offer big paying job in the Netherlands . Together with five siblings who have a variety of scientific backgrounds – some are doctors , dentists , pharmacists and economics graduate – he tried again .
This time , after initially rented a garage in the area of ​​Tanjung Priok , 6 brothers issued capital each big enough . ” Kamicommitted because then bought the building in Tanjung Priok so no way back , ” said born in Tegal , 23 September 1933 , with a laugh . “If not , we will lose . “
Commitments made ​​at the right time , we know , successful childbirth .
In 1966 , with the rise of Suharto as President who opened the door wide for the entry of foreign capital , ranks multinationals flocked to Indonesia . Pfizer , GSK and Boehringer not only bring capital but also technology . ” And the most important technologies that they bring , ” said dr . Boen earnestly , ” is … marketing . “
Boen remember very well , when it was a local company such as Incense and Soho only produce generic drugs are sold at low prices .
 Meanwhile , the champion of the world pharmaceutical industry to sell its products at high prices due to the marketing efforts are not cheap .
Given this reality , he said , ” We went in with a price in the middle position . “
Positioning at the top but the generic product under the originator ‘s product makes Kalbe can reap enough profit margins fat and still have a price advantage that allows to compete with multinational corporations .
Create boost brand created , Boen also not rely solely on marketing .
From the beginning , he incorporates elements of research and development into products Kalbe . By replacing or adding 1-2 active ingredients of the original composition of the product , he can differentiate the product . Moreover , the scientific background as a physician pharmacologists enabled him to create a rational composition .
Until now , the basic strategy is still adhered to by Kalbe . In terms of prices , for example , despite already having an extensive network of doctors , Kalbe still set prices ” at the top of a generic product , but under the product originator ” .
” On average they ( Kalbe ) set the price of the product 8 times the price of a generic drug and under the price of the originator product , ” said an executive of a national pharmaceutical company .
The director who refused to be named this call Kalmoxillin as an example . Kalbe artificial antibiotic product is priced about 8 times the price of Amoxicillin , at least before the generic product whose price is set by the government is downgraded , but still cheaper than Amoxil is an original product .
Perhaps you will ask , is there a national company that dared to set product prices , which in fact is just a cheat , higher than the original products of the pharmaceutical industry champions abroad ?
And he said no . And the product of this greedy pharmaceutical companies still find a buyer .
Understandably , the drugs we call it by the name ” S ” it is a prescription medication that is prescribed by doctors, anyone can not replace the Amoxicillin ( generic ) ,
Kalmoxillin ( branded generics are less expensive and may not necessarily be of poor quality ) , even Amoxil ( original brand ) , without the consent of the doctor who wrote the prescription .
Pharmaceutical companies are well-known greedy doctor is obviously a lot to buy quickly skyrocket . Therefore , given that the wood without messing Kalbe like it could be the biggest pharmaceutical companies , it raises its own admiration .
Another thing that is admirable , it was, courage Kalbe OTC product launches .
 Different from the ethical product purchasing decisions in the hands of a doctor , in order to be successful in the market , a drug that can be purchased without a prescription it must obtain the final consumer trust .
 Because it involves millions of his own pocket and population , the end consumer is obviously more difficult than the doctor who persuaded tens of thousands and the population is only just getting patients to buy ( and , of these transactions , he could get a big bonus ) . In addition , the price of OTC products also can not be set too high because the competition is much more free , so that the relatively low profit margins .
In short, build brand OTC products is much more difficult – takes longer and costs more – than prescription drugs . Take for example Fatigon .
Previously marketed as ethical products , multivitamins of Dankos was launched as an OTC in the mid -1990s . However , Arie Wibowo message through a new entrance into the minds of consumers in the early 2000s , so they were only able to enjoy the results in recent years .
To build OTC brands , the efforts made much longer than the existence of ad impressions that can be monitored through the television set . Long before the products are formulated , first conducted research for knowing the needs of the market . From these results – for example , some people will need medications to eliminate fatigue with a certain price range – the exact composition of the product created and developed the production process accordingly.
Products that respond to these needs, Fatigon , developed based formulations neurovitamin plus vitamin E.
 This combination is already on the market , the product has even made ​​me too it by a national pharmaceutical company .
Dankos innovation lies in the addition of potassium and magnesium salts of L – aspartate which can accelerate the dismantling of lactic acid .
 Well , because it can accelerate the dismantling of a substance which is a metabolic waste that causes muscle fatigue and communicated this Fatigon as a multivitamin to make fatigue go away ( gone ) , aka tired relievers . This ingenious Positioningyang make Fatigon able to capture 35 % market share multivitamin .
And they did not stop there . Create meremajakannya – or mengapitalisasi Fatigon name that has been built at a cost of tens of billions – Dankos develop another variant : Spirit Fatigon spiked with L- carnitine , an amino acid compound which can accelerate the burning of fat into energy .
Create distinguish it from ordinary Fatigon , product extensions which no longer contain L – aspartate salt is dressed in a bright red packaging and take Primus Yustisio as endorser .
Kalbe is good at developing brand and meremajakannya . View Promag alone . Launched in 1971 as the first stomach pain medications advertised , antacid ( neutralizing stomach acid ) this one is one of the few local products which is able to defeat the dominant products of multinational companies in almost all countries .
Bottles are Teh Bak conquer the Coca-Cola Soft Drinks Global King , Promag garnering 80 % market share of stomach pain medications , making Mylanta is popular all over the world it did not move . Ke-4/2005 quarter , according to a survey conducted by a third , with sales of Rp 33.13 billion Promag was ranked 5th best-selling drug in the ranks of drug stores .
Amazingly, Kalbe is not only able to maintain a relatively cheap Promag it . Later , they were also able to develop it into a more upper class with Promag Double Action . Then , to keep the attack from below , Kalbe use Toedjoe Star to confront the Chinese-yam which , again , has a product differentiation . Joint Chinese-yam which also controls the sale of greater than Mylanta , Kalbe holding 89 % market share of stomach pain medications .
In the category of other medicinal products , Kalbe also triumphed . Neo – Enterostop holding 48 % market share antidiarrheal medication . In kerubutan , Woods , Komix , Mixadin and controls 50 % market Mextril cough medicine . Then , as mentioned above , and Mixagrip Procold captured 40 % market share of the flu drug .
In fact , with sales of USD 8.92 billion , according to a survey conducted third party , Procold ” reformula ” which was launched in February 2004 was ranked top selling new medicines in drugstores for IV/2005 quarter , followed by Extra Joss B7 ( selling USD 6.11 billion ) which was launched in May 2005 . The new OTC products other Kalbe Group , Irex Max , which launched in July 2004 was ranked as the 7th with sales of USD 2.99 billion .
Kalbe successful launching of this OTC product range makes them hoist themselves as the most successful company sells its products through drug stores . IV/2005 quarter , the Group Kalbe reap sales of Rp 284.42 billion of free drug was the biggest outlets – leaving far its closest competitor , Pfizer Group and Tempo Group is in the same quarter each only grossed sales of Rp 177.30 billion and Rp 160.93 billion .
In the energy drink product category , with Extra Joss is holding 43 % market share , again Kalbe successful global brand memecundangi dominant everywhere . Currently , Extra Joss which is one of the biggest growth engine Kalbe has set foot in the Philippines market . In Indonesia , the products cleverly formulated in the form of effervescent powder has diekstensi so Extra Joss LG , Extra Joss Extra Joss X and Endurance .
In dairy products and other health foods , Kalbe also showed his power . Drawn Prenagen (which has over 68 % market share of dairy product categories for pregnant women ) and Diabetasol ( which is holding 51% market share clinical food product category ) as the biggest growth locomotive , in 2005 they reap sales of U.S. $ 104 million from health food – far over -the-counter as well as energy drinks , each of which only U.S. $ 88 million .
For products that can be bought , Kalbe occupy an honored place in every major category . In the category of OTC drug products , for example , with a market share of 12.7 % in 2005 Kalbe fluttering at the top , beat Tempo ( 10.4 % ) or Konimex ( 7.4 % ) were known to have a strong brand it .
In the category of energy drink products , Kalbe dominance almost impossible shaken . Extra Joss market share and its derivatives in 2005 reached 43.5 % which is much larger than the Red Bull ( 22.4 % ) and Hemaviton and its derivatives ( 12.5 % ) combined.
Only in the category of nutritional products Kalbe is holding a 10.1 % market share lost to specialist dairy products : Nestle ( 36.1 % ) and Sari Husada ( 14.4 % ) . Nevertheless, considering Kalbe mainly go into the premium market , profit margins are fatter certainly ditangguk
For ethical product category ? Kalbe still have to admit supernatural Dexa Medica and Pharma were indeed whiz Sanbe ethical products . However , control of the national market share of 9.4 % , in the categories of products should only be sold with a doctor ‘s prescription Kalbe who was ranked 3rd narrowly lost Dexa ( 12.0 % ) and Sanbe ( 10.3 % ) .
Kalbe income of ethical product category is mostly obtained through the sale of branded drug products ( 60.0 % , valued at U.S. $ 83 million ) , followed by products licensed drugs ( 29.0 % , valued at U.S. $ 41 million ) , which gives a relatively high margin . Product sales are low-margin generic drugs accounted for only 11.0 % ( worth U.S. $ 15 million ) .
If dissected according to the target market , revenue Kalbe of ethical product categories derived primarily from sales through specialist physicians ( 46 % ) , followed by general practitioners ( 21 % ) and institute ( 13 % ) . Of this target market , again the composition of high -margin sales of ethical products is very dominant . Specialists, we know , always prescribe the most expensive drugs . Meanwhile , sales to institutions normally associated with generic drugs . For non-branded drugs , market institutions provide higher profit margins than regular market in the era of regional autonomy is highly fragmented , so the high cost of marketing .
Kalbe success marketing products with high margins also reflected on their key products are relatively brand new . Subcategory of antibiotic products carrying names Cefspan , Fixef , Cravit , Reskuin , Tarivid , Danofloc , Cefizox and Cefazol . Then , no more than a subcategory produkhospital ( Fimalbumin and Octalbin ) , antineoplastic and immunomodulatory ( Paxus , epirubicin ) , musculo – skeletal system ( Mediflex ) .
Ke-4/2005 quarter , Cefspan even ranked 7th best-selling drug list with sales of Rp 19.14 billion, growing 26 % from the previous year to Rp 15.22 billion and was ranked 15th . For new drug products in pharmacies , managed to put Mediflex Kalbe ranked 8th best sellers with sales of USD 3.20 billion and Doxorubicin at No. 11 (USD 2.59 billion ) . Meanwhile , for new pharmaceutical products in hospitals , they managed to put Cernevit ( sales of USD 3.21 billion ) billion at No. 4 , followed by doxorubicin (USD 2.20 billion ) at No. 9 , epirubicin ( USD 2 billion ) at No. 12 , Fima Hes 200 ( USD 1.86 billion ) at No. 16 , and Kalbamin (USD 1.83 billion ) in the rankings to 18th .
The number of new products whose sales shot shows that Kalbe has a lot of future growth engines . ” We will regularly launches 15 new products every year , ” said Johannes Setijono , CEO of Kalbe , sure .
If the products are launched it as they had done before – at least in part based biotechnology which , because of the high – tech , very few competitors – the engine of future growth Kalbe will certainly extraordinary .
 Moreover , if the grand plan went into biogenerik products through Innogene materialize .
Understandably , in the whole world will be confirmed only a handful of pharmaceutical companies are able to produce generic biotechnology-based products that complicated .
Beyond this , in collaboration with Recombio , Innogene even develop a vaccine for cancer called 1E10 .
With anti – idiotypic cancer vaccine made ​​from mammalian cells needed this particular , breast cancer , lung cancer and skin cancer will have an effective alternative to drugs and 40 % less expensive . Another big leap pursued Kalbe Group is the product of a stem cell biotechnology .
Other growth engine , which is no less great , is selling to overseas markets . In 2005 , the export value of their drug products that Rp 294.83 billion – plus packaging (USD 7.26 billion ) and health foods ( USD 8.76 billion ) – a new portion occupies 5.2 % of the total sales . That is , the export market segments still gives a very spacious room to grow .
In 2005 , with the Orange holding Drug Ltd. . , Nigeria , Kalbe establish a joint venture . With Orange – Kalbe operation in 2007 , sales are expected Promag , Procold , Neo – Enterostop , and other Kalbe mainstay products in the West African country will exceed U.S. $ 10 million / year . For the 30 % ownership stake , Kalbe plant U.S. $ 3 million .
” But , all the equipment we send from here , anyway, ” said dr . Boen sumringah Tegalnya subtle accent . Elderly men who still energetic hope , in the next five years , exports soared Kalbe will contribute 15 % to total sales .
Joint venture with Morinaga , Kalbe which controls 70.0 % of shares is also building dairies . This step will obviously strengthen their position in the dairy business premium class . Currently, Chil Mil and its derivatives have defeated foreign premium brands in other countries generally dominate the market .
Beyond that , Kalbe presumably could also hope to develop Enseval Son Megatrading be considerable growth engine . Has 40 distribution centers that are directly or indirectly mengover 1 million outlets , trunk distribution Kalbe is the largest distributor of healthcare products in Indonesia . In 2005 , 25 % Enseval reap revenue from Eisei , Takeda , L’ Oreal , Mead Johnson and other international business partners .
With the increasing number of foreign products coming into the country , experienced Enseval poduk distributes various categories – from OTC , prescription drugs , chemicals and other raw materials to consumer products healthdan health equipment – will certainly get a chance to enlarge his business . Understandably , however , new entrants from outside is not possible to handle its own distribution elaborate .
In addition , although lagging step of Dexa , Kalbe is also developing a test lab bioavailability / bioekivalen ( BA / BE ) . Under harmonization of ASEAN market in 2008 , which requires all drugs to be distributed in Southeast Asian markets tested BA / BE , Pharma Labs built Metrics is certainly a great opportunity to become a profit center .
All of this makes Kalbe one of the few Indonesian business entities that are well- positioned in the AFTA era soon . Moreover , if the consolidation is done running smoothly . Opportunities to it ? They are quite certain, that a grand merger will be done as smoothly as planned . The reason is simple , it just happened in the merger between the parent companies who are committed to one , with the same purpose . All subsidiaries are taken each parent only needs to submit to the commitment of its parent .
For example , Star Toedjoe previously under Dankos , stay involved just what the commitment Dankos . Even if there is displacement position , said officials Kalbe , ” That was ordinary . We have often experienced the rotation . “
In metamorphosis Kalbe , what is done now to 2015 is a big stage of globalization . To that end , the expansion should be done at least to the ASEAN region . Here , because of his elephant -sized , large -sized businesses is a must . That is why , the merger is done . After the completion of internal consolidation , mergers and acquisitions will be done externally in order to stimulate growth .

Previously , the first metamorphosis ( 1966-94 ) , Kalbe been expanding rapidly in a similar way . In 1975 , for example , Kalbe establish subsidiaries outside its core business – but still related , ie Igar Jaya engaged in the packaging industry . This expansion was followed by the formation Dankos intended to enter the market further down .
Then , in 1981 , when the government requires a separate distribution business of production , Kalbe Enseval release . That same year , Kalbe parenteral preparations go into business and consumer health business venturing , each through Finusol Prima Perkasa and Biosciences .
In 1985 , Kalbe first major acquisition . Using Dankos hand , they annexed Toedjoe Star and Hexpharm . Then , in 1989 , as an exploratory step into the capital market , stock Dankos and Igar Jaya launched on the JSE and the Surabaya Stock Exchange . After that go public TEBUKTI it profitable , then the main company , Kalbe Farma , brought to the trading floor .
With stronger capital , 1993 , Kalbe Farma first consolidation : Mighty Biosciences annexed and put bisnisconsumer health subsidiary to this one . That same year , went into business Kalbe energy drinks . In 1994 , the stock turn Enseval released to the trading floor . The era of expansion led new business development and acquisition closed with the establishment of PT Bifarma Adiluhung and the launch of Extra Joss by Toedjoe Star in 1995 .
Entering 1996, the major consolidation Kalbe start by removing 50 % stake Hill manikam Sakti engaged in the food business to Arnotts . More comprehensive consolidation carried out in 1997 and thereafter when Kalbe worse by the financial crisis that hit Asia .
The fast pace back to the core business – consumer health , ethical pharmaceutical products , as well as distribution and packaging – Kalbe saved from the brink of bankruptcy . In 2005 , consumer healthyang include OTC pharmaceutical products , product nutisi and energy drinks accounted for 47 % of revenue. The rest , contributed ethical pharmaceutical products ( 23 % ) as well as distribution and packaging ( 30 % ) . A balanced portfolio is one of the pillars of strength Kalbe .
Another pillar of strength , we have referred to above , is their prowess in research & development as well as the skill and perseverance to market products , especially OTC , which they developed . Still less ?
Yes , there is one more pillar of the biggest : human resources and management professionals . Different from Lippo Ciputra Group or its management or the Salim family dikangkangi still strong , Kalbe arguably the only large conglomerates are almost fully staffed professional management .
Realizing its strength as a scientist and visionary but less control of the management of everyday business – perhaps the wisdom of two times the initial failure – dr . Boen since the beginning of setting up the management ranks of professionals to manage Kalbe . When in this country not many qualified executives , he did not hesitate to pay expensive expatriates .
Currently , management Kalbe has arguably matured . In terms of lessons learned , they may be more complete than any big company management in the country . And they managed to rise from adversity to remain the largest .
” The blow was severe , if not deadly , it will make us stronger , ” said the wise man . This power alone , plus the advantages of being a public company whose majority shares are still controlled by the family – must be transparent , but strong enough to resist the urge to minority investors are usually more concerned with short-term gains – likely to be a sufficient provision for Kalbe become big companies , even the grandest in the ASEAN region

Kamis, 01 Juni 2006
Oleh : Prih Sarnianto

Melalui merger, Kalbe Farma menyeruak ke posisi puncak jajaran perusahaan farmasi terakbarIndonesia. Apa saja kekuatan yang memungkinkan mereka jadi yang terbesar di kawasan ASEAN?

Inilah perkawinan terakbar di panggung bisnis Indonesia. Melalui merger internal itu, PT Kalbe Farma Tbk. sebagai surviving company menyalip Sanbe Farma yang selama bertahun-tahun berkibar di puncak sebagai perusahaan farmasi terbesar di Tanah Air.

Bahkan, lebih dari itu. Dengan kapitalisasi pasar US$ 2 miliar, perusahaan yang sahamnya tercatat di Bursa Efek Jakarta dengan kode KLBF ini juga memantapkan diri di peringkat teratas jajaran perusahaan publik di Asia Tenggara.

Dari segi penjualan, Kalbe hasil merger yang meraup revenueUS$ 267,2 juta, di kawasan Asia Tenggara hanya kalah dari Pfizer dan GlaxoSmithKline (GSK) yang memang raksasa industri farmasi dunia.

Kendati demikian, sebagai kelompok bisnis farmasi, Grup Kalbe sebenarnya selalu yang terbesar.

Maklum, di bawah payung kerajaan bisnis yang satu ini, secara langsung maupun tak langsung terdapat nama-nama besar, termasuk Bintang Toedjoe (produsen Extra Joss yang masuk jajaran 10 Besar Perusahaan Farmasi di Indonesia), Hexpharm (produsen obat generik terbesar ke-5 di Indonesia), Saka Farma (ingat Sakatonic ABC?), Sanghiang Perkasa (produsen Prenagen, Diabetasol, dan makanan kesehatan lainnya), Kalbe Morinaga (produsen susu terkemuka), Innogene Kalbiotech (produsen obat berbasis bioteknologi di Singapura) dan Kageo Igar Jaya (pengemas).

Merger yang melibatkan PT Enseval sebagaisuperholding dan tiga anak perusahaan yang terdaftar di BEJ tersebut  – Kalbe Farma, Dankos Laboratories (DNKS), Enseval Putera Megatrading (EPMS) — sekaligus membentuk perusahaan yang betul-betul terintegrasi. Secara horisontal, Kalbe “baru” menawarkan rentang produk yang jauh lebih luas, mulai dari berbagai bentuk obat dan makanan kesehatan sampai suplemen dan minuman berenergi. Secara vertikal, mereka melakukan kegiatan dari pengadaan bahan baku, manufakturing produk jadi, pemasaran, sampai penjualan dan distribusi.

Konsolidasi yang dilakukan, para petinggi Kalbe maupun analis meramalkan, bakal meningkatkan efisiensi operasional bisnis. Untuk pengadaan saja, penanganan yang terpusat akan membuat posisi tawar meningkat sehingga harga beli bahan baku dapat ditekan. Inventori juga bakal lebih efisien. Demikian pula, produksi yang skala ekonominya melejit.

Di sisi pemasaran, alokasi dana untuk perluasan pasar akan menggelembung sehingga pasar baru yang bisa digarap juga akan jauh lebih luas dan, buntutnya, meningkatkan daya saing. Upaya pemasaran yang dengan cerdik dibagi berdasarkan pasar dari berbagai sisi — OTC (over the counter, obat yang dapat dijual bebas, tanpa resep dokter), etikal (obat dengan resep), rumah sakit, dokter praktik, dokter spesialis, institusi — dapat dilakukan secara lebih fokus.

“Kalau perusahaannya tidak besar, melakukan ini tanggung,” ujar Herman Widjaja. Pasalnya, menurut Direktur Pemasaran Grup Kalbe ini, buat memelihara barisan tenaga penjualan yang khusus itu diperlukan biaya tambahan yang besar.

Di luar masalah efisiensi, merger yang dilakukan menghentikan “perang saudara” yang selama ini terjadi. Sebelumnya, orang-orang Kalbe dan Dankos, misalnya, karena tahu benar isi perut masing-masing, di lapangan saling jegal dengan sengit. Dengan penggabungan yang membuat mereka jadi satu tim, agresivitas di lapangan tentunya akan dapat dialihkan ke pesaing luar.

Hebatnya, walau terjadi perang saudara, Kalbe dan Dankos pramerger dapat berbagi wilayah pasar. Di kategori produk obat flu, misalnya, Procold yang membawa bendera Kalbe berkibar di Kawasan Indonesia Barat, mulai dari Jawa Tengah dan Jakarta. Sementara itu, Mixagrip yang menyandang nama Dankos kuat di Kawasan Indonesia Timur, mulai dari Jawa Timur sampai Bali, Nusa Tenggara Timur dan Sulawesi. Tak mengherankan, kedua merek ini jadi sama-sama besar dan secara agregat menguasai 40% pasar nasional.

Pemisahan pasar tersebut, menurut Herman, secara resmi tidak dirancang. Kendati demikian, katanya, “Kami, kan, melakukan marketing activity secara terfokus agar tidak meluber ke semua wilayah. Jadi, dibentuklah kantong-kantong tersebut.” Alasan di balik ini? “Agar (dalam upaya pemasaran) tidak kehabisan dana.”

Dari sisi penjualan, Mixagrip menjadi pemimpin pasar dengan pangsa sekitar 30% sehingga mengungguli Procold yang bahkan kalah dari Ultraflu (Henson farma) dan Decolgen (Medifarma).

Namun, menguasai segmen pasar yang lebih tinggi (mass affluent dan middle mass), Procold memberikan margin laba yang lebih tinggi ketimbang Mixagrip yang segmen pasarnya lebih rendah (middle massdan lower mass).

Pembagian target segmen pasar seperti ini jelas bukan merupakan kebetulan. Pada 1974, ketika Procold diluncurkan, pasar obat flu untuk segmen menengah-bawah sudah sangat sesak. Sebab itu, Kalbe lalu memosisikan Procold di atas produk lokal yang telah menguasai segmen bawah melalui persaingan harga, tetapi masih di bawah produk kampiun industri farmasi asing. Untuk segmen pasar bawah yang lebih besar — pada 2005, size pasarlower mass diperkirakan US$ 900 juta atau jauh lebih besar ketimbang pasar middle mass (US$ 400 juta), mass affluent (US$ 300 juta) ataupun affluent(US$ 400 juta) — bertahun-tahun kemudian Kalbe menjagokan Mixagrip yang diproduksi Dankos.

Didukung upaya pemasaran yang berani dan telaten,positioning yang dipasangkan secara tandem tersebut terbukti ampuh untuk merebut pasar di seluruh segmen — dari yang bawah sampai ke atas. Walau secara keseluruhan penjualan Procold hanya menduduki peringkat ke-4, untuk segmen menengah-atas produk obat flu Kalbe ini masih di atas Neozep dan sebangsanya. Dengan demikian, di satu kategori produk yang gemuk ini saja, Kalbe berhasil menciptakan dua mesin pertumbuhan yang besar.

Apa yang mereka lakukan ketika menaklukkan pasar kategori produk obat flu boleh dibilang khas Kalbe. Didirikan pada 1966, sejak awal Boenjamin Setiawan ingin menempatkan Kalbe sebagai perusahaan yang memiliki diferensiasi. Ketika mengambil program Ph.D bidang farmakologi di University of California, Boenjamin yang kala itu menjadi dosen muda di Fakultas Kedokteran Universitas Indonesia melihat peluang tumbuhnya perusahaan farmasi yang tak hanya memproduksi obat generik di Tanah Air.

“Produk yang dibuat haruslah unik, berbeda dari yang sudah ada di pasar,” tutur dr. Boen. “Dan, produk itu harus dipasarkan dengan strategi yang baik.”

Namun, walau visinya jelas, tak gampang mewujudkannya jadi sebuah bisnis. Buktinya, upaya awal yang dilakukan dr. Boen muda bersama beberapa rekan dosen FKUI gagal.

Pada 1963 itu, baru dua tahun pulang dari Amerika Serikat, kondisi sosial-ekonomi Indonesia mungkin belum kelewat kondusif untuk sebuah bisnis dengan cita-cita besar. Atau mungkin, dia dan kawan-kawan yang sesama dokter tak ada yang berpengalaman menjalankan bisnis sehingga amburadul hasilnya.

Untungnya, Boen tak putus asa walau sempat tergiur tawaran kerja bergaji gede di Belanda. Bersama lima saudaranya yang memiliki berbagai latar belakang keilmuan — ada yang dokter, dokter gigi, apoteker dan sarjana ekonomi — dia mencoba lagi.

Kali ini, setelah awalnya menyewa garasi di kawasan Tanjung Priok, 6 bersaudara itu masing-masing mengeluarkan modal cukup besar. “Kamicommitted lantaran lalu beli gedung di Tanjung Priok sehingga tak bisa mundur lagi,” tutur kelahiran Tegal, 23 September 1933, itu sambil tertawa. “Kalau tidak, kami akan rugi.”

Komitmen yang dilakukan pada saat yang tepat tersebut, kita tahu, melahirkan sukses.

Pada 1966 itu, dengan naiknya Soeharto sebagai Presiden RI yang membuka pintu lebar-lebar bagi masuknya modal asing, barisan perusahaan multinasional berbondong ke Indonesia. Pfizer, GSK dan Boehringer bukan hanya membawa modal, melainkan juga teknologi. “Dan teknologi terpenting yang mereka bawa,” ungkap dr. Boen dengan sungguh-sungguh, “adalah … marketing.”

Boen ingat betul, waktu itu perusahaan lokal seperti Dupa dan Soho hanya memproduksi obat generik yang dijual dengan harga murah.

Sementara itu, para jawara industri farmasi dunia menjual produknya dengan harga mahal karena melakukan upaya pemasaran yang tidak murah.

Melihat kenyataan ini, tuturnya, “Kami masuk dengan posisi harga di tengah.”

Positioning di atas produk generik tetapi di bawah produk originator ini membuat Kalbe dapat menangguk margin laba cukup gemuk dan tetap memiliki keunggulan harga yang memungkinkan bersaing dengan kalangan perusahaan multinasional.

Buat mendongkrak merek yang diciptakan, Boen juga tak hanya mengandalkan pemasaran.

Sejak awal, dia memasukkan unsur riset & pengembangan ke dalam produk-produk Kalbe. Dengan mengganti atau menambah 1-2 bahan aktif dari komposisi produk original, dia dapat mendiferensiasi produk. Apalagi, latar belakang keilmuannya sebagai dokter yang ahli farmakologi memungkinkannya menciptakan komposisi yang rasional.

Sampai saat ini, strategi dasar ini masih dipegang teguh oleh Kalbe. Dari sisi harga, misalnya, walau telah memiliki jaringan dokter yang luas, Kalbe tetap menetapkan harga yang “di atas produk generik, tetapi di bawah produk originator”.

“Rata-rata mereka (Kalbe) menetapkan harga produknya 8 kali harga obat generik dan di bawah harga produk originator,” ujar seorang eksekutif perusahaan farmasi nasional.

Sang direktur yang tak mau disebut namanya ini menyebut Kalmoxillin sebagai contoh. Produk antibiotik buatan Kalbe ini dibanderol sekitar 8 kali harga Amoxicillin, setidaknya sebelum produk generik yang harganya ditetapkan pemerintah ini diturunkan, tetapi masih lebih murah ketimbang Amoxil yang merupakan produk original.

Mungkin Anda akan bertanya, adakah perusahaan nasional yang berani menetapkan harga produknya, yang notabene cuma contekan, lebih tinggi ketimbang produk original dari kampiun industri farmasi mancanegara?

Jawabnya: ada. Dan produk perusahaan farmasi yang serakah ini tetap mendapatkan pembeli.

Maklum, obat yang kita sebut saja dengan nama “S” itu adalah obat etikal yang diresepkan dokter, siapa pun tak boleh mengganti dengan Amoxicillin (generik),

Kalmoxillin (generik bermerek yang lebih murah dan belum tentu lebih jelek kualitasnya), bahkan Amoxil (merek original), tanpa persetujuan dokter yang menulis resep tersebut.

Perusahaan farmasi serakah yang terkenal banyak membeli dokter ini jelas cepat meroket. Karena itu, menilik bahwa Kalbe tanpa main kayu seperti itu bisa jadi perusahaan farmasi terbesar, sungguh menimbulkan kekaguman tersendiri.

Hal lain yang patut diacungi jempol adalah, itu tadi, keberanian Kalbe meluncurkan produk OTC.

Berbeda dari produk etikal yang keputusan belinya ada di tangan dokter, agar sukses di pasar, obat yang dapat dibeli tanpa resep itu harus memperoleh kepercayaan konsumen akhir.

Karena menyangkut kocek sendiri dan populasinya jutaan, konsumen akhir jelas lebih sulit dibujuk ketimbang dokter yang populasinya hanya puluhan ribu dan sekadar menyuruh pasien untuk beli (lalu, dari transaksi tersebut, dia bisa mendapat bonus gede). Selain itu, harga produk OTC juga tak dapat ditetapkan kelewat tinggi karena persaingannya jauh lebih bebas, sehingga margin labanya relatif rendah.

Pendek kata, membangun merek produk OTC jauh lebih sulit — makan waktu lebih lama dan biaya lebih banyak — ketimbang obat etikal. Ambil contoh Fatigon.

Sebelumnya dipasarkan sebagai produk etikal, multivitamin dari Dankos ini diluncurkan sebagai OTC pada pertengahan 1990-an. Namun, pesan melalui Arie Wibowo baru masuk ke benak konsumen pada awal 2000-an, sehingga mereka baru bisa menikmati hasilnya beberapa tahun belakangan.

Untuk membangun merek OTC, upaya yang dilakukan jauh lebih panjang ketimbang adanya tayangan iklan yang bisa dipantau melalui pesawat televisi. Jauh sebelum produk diformulasikan, dilakukan dulu penelitian buat mengetahui kebutuhan pasar. Dari hasil penelitian ini — misalnya, kebutuhan sebagian masyarakat akan obat yang dapat menghilangkan kelelahan dengan kisaran harga tertentu — diciptakan komposisi produk yang tepat dan dikembangkan proses produksi yang sesuai.

Produk yang menjawab kebutuhan ini, Fatigon, dikembangkan berdasarkan formulasi neurovitamin plus vitamin E.

Kombinasi ini sudah ada di pasar, bahkan sudah dibuat produk me too-nya oleh sebuah perusahaan farmasi nasional.

Inovasi Dankos terletak pada penambahan garam kalium dan magnesium dari L-aspartat yang dapat mempercepat pembongkaran asam laktat.

Nah, karena bisa mempercepat pembongkaran zat yang merupakan sisa metabolisme yang menimbulkan lelah otot inilah Fatigon lalu dikomunikasikan sebagai multivitamin untuk membuat fatigue pergi (gone), alias obat penghilang lelah. Positioningyang cerdik ini membuat Fatigon mampu merebut 35% pangsa pasar multivitamin.

Dan mereka tak berhenti sampai di situ. Buat meremajakannya — atau mengapitalisasi nama Fatigon yang telah dibangun dengan biaya puluhan miliaran — Dankos mengembangkan varian lain: Fatigon Spirit yang dibubuhi L-carnitin, senyawa asam amino yang dapat mempercepat pembakaran lemak menjadi energi.

Buat membedakannya dari Fatigon biasa, produk ekstensi yang tak lagi mengandung garam L-aspartat ini didandani dengan kemasan merah menyala dan mengambil Primus Yustisio sebagai endorser.

Kalbe memang piawai mengembangkan merek dan meremajakannya. Lihat saja Promag. Diluncurkan pada 1971 sebagai obat nyeri lambung pertama yang diiklankan, antasida (penetral asam lambung) yang satu ini adalah satu dari sedikit produk lokal yang mampu mengalahkan produk perusahaan multinasional yang dominan di hampir semua negara.

Bak Teh Botol yang menaklukkan Coca-Cola sang Raja Minuman Ringan Global, Promag meraup 80% pangsa pasar obat nyeri lambung, membuat Mylanta yang ngetop di seluruh penjuru dunia itu tak berkutik. Pada kuartal ke-4/2005, menurut survei yang dilakukan pihak ketiga, dengan penjualan Rp 33,13 miliar Promag menduduki peringkat ke-5 jajaran obat terlaris di toko-toko obat.

Hebatnya lagi, Kalbe bukan cuma mampu mempertahankan Promag yang harganya relatif murah itu. Belakangan, mereka juga mampu mengembangkannya ke kelas yang lebih atas dengan Promag Double Action. Lalu, untuk menjaga serangan dari bawah, Kalbe menggunakan Bintang Toedjoe untuk menghadang dengan Waisan yang, lagi-lagi, memiliki diferensiasi produk. Bersama Waisan yang juga menguasai penjualan lebih besar ketimbang Mylanta, Kalbe menggenggam 89% pangsa pasar obat nyeri lambung.

Di kategori produk obat lainnya, Kalbe juga berjaya. Neo-Enterostop menggenggam 48% pangsa pasar obat antidiare. Secara kerubutan, Woods, Komix, Mixadin dan Mextril menguasai 50% pasar obat batuk. Lalu, seperti yang telah disebutkan di atas, Procold dan Mixagrip merebut 40% pangsa pasar obat flu.

Bahkan, dengan penjualan Rp 8,92 miliar, menurut survei yang dilakukan pihak ketiga, Procold “reformula” yang diluncurkan pada Februari 2004 menduduki peringkat puncak obat-obat baru terlaris di toko obat untuk kuartal IV/2005, disusul Extra Joss B7 (penjualan Rp 6,11miliar) yang diluncurkan pada Mei 2005. Produk OTC baru Grup Kalbe lainnya, Irex Max, yang diluncurkan pada Juli 2004 menempati peringkat ke-7 dengan penjualan Rp 2,99 miliar.

Sukses Kalbe meluncurkan berbagai produk OTC ini membuat mereka mengibarkan diri sebagai perusahaan yang paling sukses menjual produknya melalui toko obat. Pada kuartal IV/2005, Grup Kalbe meraup penjualan Rp 284,42 miliar dari gerai terbesar obat bebas itu — meninggalkan jauh pesaing terdekatnya, Grup Pfizer dan Grup Tempo yang pada kuartal yang sama masing-masing hanya meraup penjualan Rp 177,30 miliar dan Rp 160,93 miliar.

Di kategori produk minuman berenergi, dengan Extra Joss yang menggenggam 43% pangsa pasar, lagi-lagi Kalbe berhasil memecundangi merek global yang dominan di mana-mana. Saat ini, Extra Joss yang merupakan salah satu motor pertumbuhan terbesar Kalbe telah menancapkan kaki di pasar Filipina. Di Indonesia, produk yang dengan cerdik diformulasikan dalam bentuk serbuk effervescent ini telah diekstensi jadi Extra Joss LG, Extra Joss X dan Extra Joss Endurance.

Di produk susu dan makanan kesehatan lainnya, Kalbe juga menunjukkan kesaktiannya. Dihela Prenagen (yang menguasai 68% pangsa pasar kategori produk susu untuk ibu hamil) dan Diabetasol (yang menggenggam 51% lebih pangsa pasar kategori produk clinical food) sebagai lokomotif pertumbuhan terbesar, pada 2005 mereka menangguk penjualan US$ 104 juta dari makanan kesehatan — jauh di atas obat OTC maupun minuman berenergi yang masing-masing hanya US$ 88 juta.

Untuk produk-produk yang dapat dibeli bebas ini, Kalbe menduduki tempat terhormat di setiap kategori besar. Di kategori produk obat OTC, misalnya, dengan pangsa pasar 12,7% Kalbe pada 2005 berkibar di puncak, mengalahkan Tempo (10,4%) ataupun Konimex (7,4%) yang dikenal memiliki banyak merek kuat itu.

Di kategori produk minuman berenergi, dominasi Kalbe bahkan hampir mustahil digoyahkan. Pangsa pasar Extra Joss dan turunannya pada 2005 yang mencapai 43,5% jauh lebih besar ketimbang Kratingdaeng (22,4%) dan Hemaviton beserta turunannya (12,5%) digabung jadi satu.

Hanya di kategori produk nutrisi Kalbe yang menggenggam 10,1% pangsa pasar kalah dari spesialis produk susu: Nestle (36,1%) dan Sari Husada (14,4%). Kendati demikian, mengingat Kalbe terutama masuk ke pasar premium, margin laba yang ditangguk tentu lebih gemuk

Untuk kategori produk etikal? Kalbe masih harus mengakui kesaktian Dexa Medica dan Sanbe Farma yang memang jagoan produk etikal. Akan tetapi, menguasai 9,4% pangsa pasar nasional, di kategori produk yang hanya boleh dijual dengan resep dokter ini Kalbe yang menduduki peringkat ke-3 kalah tipis dari Dexa (12,0%) dan Sanbe (10,3%).

Pendapatan Kalbe dari kategori produk etikal ini sebagian besar diperoleh melalui penjualan produk obat bermerek (60,0%, senilai US$ 83 juta), disusul produk obat lisensi (29,0%, senilai US$ 41 juta), yang memberikan margin relatif tinggi. Penjualan produk obat generik yang bermargin rendah hanya menyumbang 11,0% (senilai US$ 15 juta).

Jika dibedah menurut target pasar, pendapatan Kalbe dari kategori produk etikal terutama diperoleh dari penjualan melalui dokter spesialis (46%), disusul dokter umum (21%) dan insititusi (13%). Dari target pasar ini, lagi-lagi komposisi penjualan produk etikal bermargin tinggi sangat dominan. Dokter spesialis, kita tahu, selalu memberikan resep obat-obat yang termahal. Sementara itu, penjualan ke institusi biasanya terkait dengan obat generik. Untuk obat tanpa merek, pasar institusi memberikan margin laba yang lebih tinggi ketimbang pasar reguler yang di era otonomi daerah ini sangat terfragmentasi, sehingga biaya pemasarannya tinggi.

Keberhasilan Kalbe memasarkan produk dengan margin tinggi juga tecermin pada produk kunci mereka yang relatif gres. Dari subkategori produk antibiotik tercatat nama-nama Cefspan, Fixef, Cravit, Reskuin, Tarivid, Danofloc, Cefizox dan Cefazol. Lalu, ada lagi dari subkategori produkhospital (Fimalbumin dan Octalbin), antineoplastik dan imunomodulator (Paxus, Epirubicin), musculo-skeletal system (Mediflex).

Pada kuartal ke-4/2005, Cefspan bahkan menduduki peringkat ke-7 daftar obat terlaris dengan penjualan Rp 19,14 miliar atau tumbuh 26% dari tahun sebelumnya yang hanya Rp 15,22 miliar dan menduduki peringkat ke-15. Untuk produk obat baru di apotek, Kalbe berhasil menempatkan Mediflex di peringkat ke-8 terlaris dengan penjualan Rp 3,20 miliar dan Doxorubicin di peringkat ke-11 (Rp 2,59 miliar). Sementara itu, untuk produk obat baru di rumah sakit, mereka berhasil menempatkan Cernevit (penjualan Rp 3,21 miliar) miliar di urutan ke-4, disusul Doxorubicin (Rp 2,20 miliar) di peringkat ke-9, Epirubicin (Rp 2 miliar) di peringkat ke-12, Fima Hes 200 (Rp 1,86 miliar) di peringkat ke-16, dan Kalbamin (Rp 1,83 miliar) di peringkat ke-18.

Banyaknya produk baru yang penjualannya melesat ini menunjukkan bahwa Kalbe memiliki banyak mesin pertumbuhan masa depan. “Kami akan rutin meluncurkan 15 produk baru setiap tahun,” ujar Johannes Setijono, CEO Kalbe, yakin.

Jika produk-produk yang diluncurkan tersebut seperti yang sudah-sudah — paling tidak sebagiannya berbasis bioteknologi yang, karena high-tech, sangat sedikit pesaingnya — mesin pertumbuhan masa depan Kalbe tentu akan luar biasa.

Apalagi, jika rencana besar masuk ke produk biogenerik melalui Innogene terwujud.

Maklum, di seluruh dunia dipastikan hanya akan ada segelintir perusahaan farmasi yang mampu menghasilkan produk generik berbasis bioteknologi yang rumit itu.

Di luar ini, bekerja sama dengan Recombio, Innogene bahkan mengembangkan vaksin untuk kanker yang disebut 1E10.

Dengan anti-idiotypic cancer vaccine yang dibuat dari sel mamalia yang diperlukan khusus ini, penderita kanker payudara, kanker paru dan kanker kulit akan memiliki obat alternatif yang efektif dan 40% lebih murah. Lompatan besar lain yang diupayakan Grup Kalbe adalah produk bioteknologi dari stem cell.

Mesin pertumbuhan lainnya, yang tak kalah besar, adalah penjualan ke pasar mancanegara. Pada 2005, nilai ekspor produk obat mereka yang Rp 294,83 miliar — ditambah kemasan (Rp 7,26 miliar) dan makanan kesehatan (Rp 8,76 miliar) — baru menempati porsi 5,2% dari penjualan total. Artinya, segmen pasar ekspor masih memberikan ruang yang sangat luas untuk tumbuh.

Pada 2005, dengan menggandeng Orange Drug Ltd., Nigeria, Kalbe mendirikan perusahaan patungan. Dengan beroperasinya Orange-Kalbe pada 2007, diharapkan penjualan Promag, Procold, Neo-Enterostop, dan produk andalan Kalbe lainnya di negara Afrika Barat itu akan menembus US$ 10 juta/tahun. Untuk kepemilikan 30% saham, Kalbe menanam US$ 3 juta.

“Tapi, semua peralatan kami kirim dari sini, kok,” ujar dr. Boen sumringah dengan logat Tegalnya yang kentara. Lelaki sepuh yang masih energik ini berharap, dalam lima tahun ke depan, ekspor Kalbe akan melejit hingga menyumbang 15% penjualan total.

Berpatungan dengan Morinaga, Kalbe yang menguasai 70,0% saham juga sedang membangun pabrik susu. Langkah ini jelas akan memperkuat posisi mereka di bisnis persusuan kelas premium. Saat ini saja, Chil Mil dan turunannya telah mengalahkan merek-merek premium asing yang di negara lain umumnya mendominasi pasar.

Di luar itu, Kalbe agaknya juga bisa berharap mengembangkan Enseval Putera Megatrading menjadi mesin pertumbuhan yang cukup besar. Memiliki 40 pusat distribusi yang secara langsung maupun tak langsung mengover 1 juta gerai, belalai distribusi Kalbe ini adalah distributor produk kesehatan terbesar di Indonesia. Pada 2005, Enseval menangguk 25% pendapatannya dari Eisei, Takeda, L’Oreal, Mead Johnson dan mitra bisnis internasional lainnya.

Dengan semakin banyaknya produk mancanegara yang masuk ke Tanah Air, Enseval yang berpengalaman mendistribusikan berbagai kategori poduk — dari OTC, obat etikal, bahan kimia dan bahan baku lainnya sampai produk consumer healthdan peralatan kesehatan – tentu akan mendapat peluang memperbesar bisnisnya. Maklum, bagaimanapun, pendatang baru dari luar tak mungkin menangani sendiri distribusi yang rumit itu.

Selain itu, walau tertinggal selangkah dari Dexa, Kalbe juga sedang mengembangkan laboratorium uji bioavailabilitas/bioekivalen (BA/BE). Di bawah harmonisasi pasar ASEAN pada 2008 yang mewajibkan seluruh obat yang akan diedarkan di pasar Asia Tenggara lulus uji BA/BE, Pharma Metrics Labs yang dibangun ini tentu berpeluang besar menjadi profit center.

Semua ini menjadikan Kalbe satu dari sedikit entitas bisnis Indonesia yang well-positioned di era AFTA yang tak lama lagi. Terlebih, jika konsolidasi yang dilakukan berjalan mulus. Peluang untuk itu? Mereka yakin benar, merger akbar yang dilakukan akan semulus yang direncanakan. Alasannya sederhana, merger itu hanya terjadi di antara perusahaan induk yang berkomitmen menjadi satu, dengan tujuan sama. Seluruh anak perusahaan yang dibawa masing-masing induk hanya perlu tunduk pada komitmen induknya.

Sebagai contoh, Bintang Toedjoe yang sebelumnya di bawah Dankos, tinggal ikut saja apa yang menjadi komitmen Dankos. Kalaupun ada perpindahan posisi, ujar para petinggi Kalbe, “Itu sudah biasa. Kami sudah sering mengalami rotasi.”

Dalam metamorfosis Kalbe, apa yang dilakukan sekarang sampai 2015 adalah tahapan besar globalisasi. Untuk itu, harus dilakukan ekspansi setidaknya ke kawasan ASEAN. Di sini, karena lawannya berukuran gajah, ukuran bisnis yang besar merupakan keharusan. Itu sebabnya, merger dilakukan. Setelah konsolidasi internal rampung, akan dilakukan merger dan akuisisi eksternal guna memacu pertumbuhan.

 

Sebelumnya, pada metamorfosis pertama (1966-94), Kalbe pernah melakukan ekspansi cepat dengan cara serupa. Pada 1975, misalnya, Kalbe mendirikan anak perusahaan di luar bisnis inti — tetapi masih berhubungan, yaitu Igar Jaya yang bergerak di industri pengemasan. Ekspansi ini diikuti dengan pembentukan Dankos yang dimaksudkan untuk masuk ke pasar lebih bawah.

Lalu, 1981, ketika pemerintah mengharuskan bisnis distribusi terpisah dari produksi, Kalbe melepas Enseval. Tahun itu juga, Kalbe masuk ke bisnis sediaan parenteral dan merambah bisnis consumer health, masing-masing melalui Finusol Prima dan Sanghiang Perkasa.

Pada 1985, Kalbe melakukan akuisisi besar pertama. Menggunakan tangan Dankos, mereka mencaplok Bintang Toedjoe dan Hexpharm. Lalu, pada 1989, sebagai langkah penjajakan ke pasar modal, saham Dankos dan Igar Jaya diluncurkan di BEJ dan Bursa Efek Surabaya. Setelah tebukti bahwa go public itu menguntungkan, barulah perusahaan utama, Kalbe Farma, dibawa ke lantai bursa.

Dengan modal lebih kuat, 1993, Kalbe Farma melakukan konsolidasi pertama: mencaplok Sanghiang Perkasa dan menempatkan bisnisconsumer health ke anak perusahaan yang satu ini. Tahun itu juga, Kalbe masuk ke bisnis minuman berenergi. Pada 1994, giliran saham Enseval diluncurkan ke lantai bursa. Era ekspansi yang dimotori pengembangan bisnis baru dan akuisisi ditutup dengan pendirian PT Bifarma Adiluhung dan peluncuran Extra Joss oleh Bintang Toedjoe pada 1995.

Memasuki 1996, Kalbe memulai konsolidasi besar dengan melepas 50% saham Bukit Manikam Sakti yang bergerak di bisnis makanan ke Arnotts. Konsolidasi yang lebih komprehensif dilakukan pada 1997 dan sesudahnya ketika Kalbe terpuruk oleh krisis moneter yang melanda Asia.

Langkah cepat kembali ke bisnis inti – consumer health, produk farmasi etikal, serta distribusi dan pengemasan — berhasil menyelamatkan Kalbe dari jurang kebangkrutan. Pada 2005, consumer healthyang meliputi produk farmasi OTC, produk nutisi dan minuman berenergi menyumbang 47% pendapatan. Sisanya, disumbang produk farmasi etikal (23%) serta distribusi dan pengemasan (30%). Portofolio yang seimbang ini merupakan salah satu pilar kekuatan Kalbe.

Pilar kekuatan lain, yang telah kita sebut di atas, adalah kehebatan mereka dalam riset & pengembangan serta kepiawaian dan keuletan memasarkan produk, terutama OTC, yang mereka kembangkan. Masih kurang?

Ya, ada satu lagi pilar terbesar: sumber daya manusia dan manajemen yang profesional. Berbeda dari Grup Ciputra atau Lippo atau Salim yang manajemennya masih kuat dikangkangi keluarga, Kalbe boleh dibilang satu-satunya konglomerat besar yang hampir sepenuhnya dikelola manajemen profesional.

Menyadari kekuatannya sebagai seorang saintis dan visioner tetapi kurang menguasai pengelolaan bisnis sehari-hari — mungkin ini hikmah dari dua kali kegagalan awalnya — dr. Boen sejak awal menyiapkan barisan manajemen profesional untuk mengelola Kalbe. Ketika di negeri ini belum banyak eksekutif yang mumpuni, dia bahkan tak segan membayar mahal ekspatriat.

Saat ini, manajemen Kalbe boleh dibilang telah matang. Dari segi pelajaran yang diambil, mereka mungkin lebih komplet ketimbang manajemen perusahaan besar mana pun di Tanah Air. Dan mereka berhasil bangkit dari keterpurukan untuk tetap jadi yang terbesar.

“Pukulan berat itu, kalau tak mematikan, akan membuat kita lebih kuat,” begitu kata orang bijak. Kekuatan ini saja, ditambah keuntungan menjadi perusahaan publik yang saham mayoritasnya masih dikuasai keluarga — harus transparan, tetapi cukup kuat untuk menahan keinginan investor minoritas yang biasanya lebih mementingkan keuntungan jangka pendek — agaknya cukup menjadi bekal bagi Kalbe menjadi perusahaan besar, bahkan terakbar di kawasan ASEAN.

URL : http://202.59.162.82/swamajalah/sajian/details.php?cid=1&id=4427

 

 

LIPI Biotechnology Research Center in collaboration with PT . Kalbe Farma Tbk held a meeting which was held on February 7, 2014 . The event was held in the auditorium of the Research Center for Biotechnology LIPI , Cibinong attended by 62 people from LIPI and Kalbe Farma .

Head of LIPI Biotechnology Research Center (Dr. Ir . Witjaksono , M.Sc ) in the opening of the event emphasized the importance of cooperation with the private sector .
Cooperation is supported by science , technology , equipment , human resources are formidable , networks and biodiversity that we have to be very fundamental role in doing good cooperation . Besides synergistic cooperation with the private sector is an appreciation of this sort of research capability in the country .
 
The first session of the event speakers from PT . Kalbe Farma ( Mr. Ahmad R. Utomo , PhD and Mr. Indra Bachtiar , PhD ) and the next session speakers from LIPI Biotechnology Research Center (Dr. Wien Kusharyoto , Dr. . Adi Santoso , Dr. . Abd M.Fuad , Dr. . Ratih Asmana Ningrum , Dr . Sukma Nuswantara ) . Last Session at the event to present three (3 ) speakers Dr . Andria Agusta from LIPI and Biological Research Center of Bioteknonologi LIPI Research Center (Dr. and Dr. Yantyati Widyastuti . Puspita Lisdiyanti ) .
Indra Bachtiar , PhD from PT . Kalbe Farma in his presentation on stem cell pertaining to the extent of the use of stem cells in medicine .
It can be used to treat various types of diseases , stem cells can also be used for medicinal beauty .
On this occasion Dr discussion session . Sukma Nuswantara posed the question whether man-made stem cells can be packed in capsules and swallowed by the patient after stem cells can serve as treatment with stem cells in general .

Questions are answered by Mr. Indra Bachtiar , Ph.D. which says that in cold conditions stemcell we can not survive more than 5 ( five ) hours .
 So even if the capsule has benefits , contained in a capsule that is certainly not a stem cell but is most likely a protein that may stimulate the cells in our body .
Metrotvnews.com , Jakarta : Stem cell therapy is believed to harbor great potential for treating a variety of diseases in the future .
This is related to the nature of stem cells capable of shape-shifting into any organ .

Not surprisingly , at this time , almost all of the global pharmaceutical companies seeking to develop stem cell products .

In Indonesia , Kalbe Farma pharmaceutical companies participate through its subsidiary ,
Stem Cell and Cancer Institute ( SCI ) .

According to principal investigator SCI Yuyus Kusnadi , one of SCI research being done is the development of stem cells from umbilical cord tissue baby .

” Based on our research , stem cells from umbilical cord tissue much better than stem cells from umbilical cord blood , ” said Yuyus at Iftar Kalbe Farma , some time ago .

Citing research results , Yuyus explained that stem cells obtained from the blood , including umbilical cord blood of infants , ideally used to treat diseases associated with blood , such as leukemia .

As for diseases associated with organ damage , such as osteoarthritis ( wear of cartilage ) , fracture , stroke , and kidney failure should ideally be treated with stem cells originally not of blood ( type of mesenchymal stem cells ) .

Mesenchymal stem cells can be obtained from the spinal cord .
However , making the spinal cord that is invasive and can only be done by competent medical personnel often complicate special .

That’s one reason the SCI develop mesenchymal stem cells from umbilical cord tissue .

Practice, further Yuyus , newborn umbilical cord is taken approximately 1 cm . ” Selected section closest to the placenta , because it is good . “

Furthermore , umbilical cord tissue was processed in the laboratory to be taken puncanya cells .

Stem cells and cultured according to the dosage needed for later use in therapy . Later , the therapy is allogeneic . That is , patients given stem cells taken from others .

” At present , a new study early stages , will be followed by testing on animals , if successful will be forwarded to clinical trials in humans , ” said Yuyus . ( MI )

Editor : Basuki Eka Purnama

 

Pusat Penelitian Bioteknologi LIPI bekerjasama dengan PT. Kalbe Farma, Tbk menyelenggarakan pertemuan yang dilaksanakan pada tanggal 7 Februari 2014. Acara tersebut digelar di Auditorium Puslit Bioteknologi LIPI, Cibinong dihadiri 62 orang dari LIPI dan Kalbe Farma.

Kepala Pusat Penelitian Bioteknologi LIPI (Dr. Ir. Witjaksono, M.Sc) dalam pembukaan acara tersebut menekankan pentingnya kerjasama dengan pihak swasta.

Kerjasama yang disupport oleh sains, teknologi, peralatan, sumber daya manusia yang tangguh, network dan biodiversity yang kita miliki akan sangat fundamental peranannya dalam melakukan kerjasama yang baik. Disamping itu kerjasama yang sinergis dengan swasta semacam ini adalah bentuk apresiasi kemampuan peneliti dalam negeri.

Session pertama acara tersebut menghadirkan pembicara dari PT. Kalbe Farma (Bapak Ahmad R. Utomo, PhD dan Bapak Indra Bachtiar, PhD) dan session berikutnya menghadirkan pembicara dari Pusat Penelitian Bioteknologi LIPI (Dr. Wien Kusharyoto, Dr. Adi Santoso, Dr. Asrul M.Fuad, Dr. Ratih Asmana Ningrum, Dr. Sukma Nuswantara). Session terakhir dalam acara tersebut menghadirkan 3 (tiga) orang pembicara Dr. Andria Agusta dari Pusat Penelitian Biologi LIPI dan dari Pusat Penelitian Bioteknonologi LIPI (Dr. Yantyati Widyastuti dan Dr. Puspita Lisdiyanti).

Bapak Indra Bachtiar, PhD dari PT. Kalbe Farma dalam presentasinya tentang stem cell menyinggung tentang luasnya penggunaan stem cell dalam dunia kedokteran.

Selain dapat digunakan untuk mengobati berbagai macam jenis penyakit, stem cell juga dapat digunakan untuk obat kecantikan.

Pada kesempatan diskusi session ini Dr. Sukma Nuswantara melontarkan pertanyaan apakah stem cell yang dibuat manusia dapat dikemas dalam kapsul dan setelah di telan oleh pasien stem cell tersebut dapat berfungsi sebagaimana pengobatan dengan stem cell pada umumnya.

 

 

Pertanyaan tersebut dijawab oleh Bapak Indra Bachtiar, Ph.D. yang mengatakan bahwa dalam kondisi dingin stemcell kita ini tidak bisa bertahan lebih dari 5 (lima) jam.

Jadi kalaupun kapsul tersebut mempunyai manfaat, yang terdapat dalam kapsul itu tentu bukan stem cell tapi kemungkinan besar adalah protein yang mungkin dapat menstimulasi sel dalam tubuh kita.

Metrotvnews.com, Jakarta: Terapi sel punca diyakini memendam potensi besar untuk mengobati beragam penyakit di masa depan.

Hal itu terkait dengan sifat sel punca yang mampu berubah bentuk menjadi organ tubuh apa pun.

Tidak mengherankan, saat ini, hampir semua perusahaan farmasi global berupaya mengembangkan produk sel punca.

Di Indonesia, perusahaan farmasi Kalbe Farma turut ambil bagian melalui anak perusahaannya,

Stem Cell and Cancer Institute (SCI).


Menurut peneliti utama SCI Yuyus Kusnadi, salah satu penelitian yang tengah dilakukan SCI adalah pengembangan sel punca dari jaringan tali pusat bayi.

“Berdasarkan penelitian kami, sel punca dari jaringan tali pusat jauh lebih baik daripada sel punca dari darah tali pusat,” ujar Yuyus pada acara buka puasa bersama Kalbe Farma, beberapa waktu lalu.

Dengan mengutip hasil-hasil penelitian, Yuyus menjelaskan bahwa sel punca yang diperoleh dari darah, termasuk darah tali pusat bayi, idealnya digunakan untuk mengobati penyakit-penyakit yang terkait dengan darah, seperti leukemia.

Adapun untuk penyakit-penyakit yang terkait dengan kerusakan organ, seperti osteoartritis (ausnya tulang rawan), patah tulang, stroke, dan gagal ginjal idealnya diterapi dengan sel punca yang asalnya bukan dari darah (sel punca jenis mesenkimal).

 

Sel punca mesenkimal bisa diperoleh dari sumsum tulang belakang.

Namun, pengambilan sumsum tulang belakang yang bersifat invasif dan hanya bisa dilakukan oleh tenaga medis berkompetensi khusus kerap menjadi penyulit.

 

Itulah yang menjadi salah satu alasan SCI mengembangkan sel punca mesenkimal dari jaringan tali pusat.

Praktiknya, lanjut Yuyus, tali pusat bayi baru lahir diambil sekitar 1 cm. “Dipilih bagian yang terdekat dengan plasenta, karena lebih bagus.”

Selanjutnya, jaringan tali pusat itu diolah di laboratorium untuk diambil sel puncanya.

 

Sel punca lalu dibiakkan sesuai dosis yang dibutuhkan untuk kemudian digunakan dalam terapi. Nantinya, terapi bersifat alogenik. Artinya, pasien diberi sel punca yang diambil dari orang lain.

“Saat ini, penelitian baru tahap awal, nantinya akan disusul dengan ujicoba kepada hewan, kalau berhasil akan diteruskan dengan uji klinis pada manusia,” terang Yuyus. (MI)

 

 

 

Editor: Basuki Eka Purnama

 

 

 

 

 

 

 

 

 

 

 

Kebijakan Menteri Riset Dan Teknologi

The Indonesia Menistry Reaseach And Development have starting to built th Science Parks in order to get theinteraction between the REseachers in the world , traders and Government but this project have develoed in many years agot but not advanced

With the moving of the world economic from western to Asia , Indonesian must use this momentum maximaly

The Government target are

TO STIMULATING INOVATION,REASEACHING AND CREATIVATION

With the giving of tax incentive for that field

 

Dr Iwan Notes

Science Parlks too broad notion example we see the difficulties faced by Prof. Sangkot Marzuki of the Eijkman institute that examines the broad aspects of gene and disease that so much so that no visible results, see Pusdokkes Indonesian National Police Department has succeeded with its DVI DNA, according to the opinion of Dr. Iwan preferably in ranging from scientific research that is most needed at this time as
Stem cell gene Biological Research Center

 

Gagasan Science Parks terlalu luas contohnya kita lihat kesulitan yang dihadapi Prof Sangkot Marzuki dengan lembaga Eijkman yang meneliti terlau luas aspek gen dan penyakit yang jumlahya sangat banyak sehingga tidak kelihatan hasilnya ,lihat pusdokkes POLRI telah berhasil dengan DNA DVI nya ,menurut pendapat Dr Iwan sebaiknya di mulai dari penelitian ilmiah yang paling diperlukan saat ini seperti

Gen Biological stem cell Research center

 

Danny Halim , dr . ( researchers Stem Cell Research Working Group – ubuntu , members of the Association of Indonesian Stem Cells ( ASPI ) )
- Harry Murti , S.Si. ( Researchers in the Stem Cell and Cancer Institute ( SCI ) , a member ASPI )
- Ferry Sandra , drg , PhD , LFIBA ( SCI founder , co-founder of ASPI , SCI Director & Chairman of the Executive Board ASPI )
- Prof . Arief Boediono , DVM , PhD ( Professor of IPB , IPB researchers in particular fields of parthenogenesis , governing board ASPI )
- Dr . Tono Djuwantono , dr , SpOG ( K ) ( consultant fertility & reproductive endocrinology ubuntu , researchers at the Stem Cell Research Working Group – ubuntu , members ASPI )
- Boenjamin Setiawan , dr , PhD ( founder of SCI with Sandra Ferry , one of the founders of ASPI )

Disclosure of privileged number of potential stem cell ( stem cells ) in the late 20th century is a major phenomenon in the world of medicine . With its characteristics , stem cell -based medical technology promises hope of a total cure for patients with degenerative diseases such as stroke , Alzheimer’s , diabetes mellitus , Parkinson’s , and heart failure .

Stem Cell – Basic Theory & Clinical Application This is a book that presents a reliable scientific explanation of the basic theories that underlie the use of stem cells in the clinical world .

TABLE OF CONTENTS
Chapter 1
Definitions and Basic Stem Cell Biology
- Stem Cell Characteristics
- Types of Stem Cell

Chapter 2
Diversity of Stem Cell Type : Sources , Isolation Technique , Kulturisasi , Differentiation , and Kriopreservasinya
- Embryonic Stem Cell : Sources & Engineering isolation
- Adult Stem Cell source , identification , and isolation techniques
- Induction of Stem Cell Results ( Induced Pluripotent Stem Cell , iPS )
- Stem Cell Type Other : Fetal Stem Cell and Cancer Stem Cell
- Kulturisasi and Stem Cell Differentiation in In Vitro
- Keep Frozen ( Stem Cell Cryopreservation )

Chapter 3
Mechanism In Stem Cell Regeneration
- Homing
- Mechanism Regeneration by Stem Cell Network
- The use of Stem Cell in Chapter 4 Potential Gene Therapy in the World Stem Cell Research and Clinical Applications
- Aging ( Aging )
- Organ Transplant Exit For Degenerative Diseases
- New Hope For Cell Transplant Patients with Degenerative Diseases
- Role in Stem Cell Therapy Degenerative Diseases
- Role of Stem Cell in Degenerative Disease Diagnosis

SPECIFICATIONS
Year of Publication : 2010
Field of Study : Medicine ( General , Dental , Animal ) , Biology , Pharmacy
Book Size : 15.7 x 24 cm
Hlm Number : 160
Color : Full Color
Paper : HVS 70 g
Cover : Hardcover
Book Code : 0076100030
ISBN : 978-979-075-330-3
   

 Application of a modified method for the isolation of stem cells from lipoaspirates in a basic lab
Caroline T. Sardjono1 , 2 , Melina Setiawan1 , Frisca1 , Virgi Saputra3 , gwendy Aniko4 , Ferry Sandra1

1 Stem Cell and Cancer Institute
2 Microbiology Department , Faculty of Medicine , Maranatha Christian University , Bandung , Indonesia
3 Kalbe Farma Tbk
4 Mitra Kemayoran Family
abstract
The purpose Lipoaspirate containing mesenchymal stem cell numbers are much , so lipoaspirate now become a source of mesenchymal stem cells with huge potential for research and for clinical applications . Simple method mesenchymal stem cell isolation that can be applied on the basis of the laboratory will facilitate the development of stem cell research in developing countries . Hopefully, the results of this study can enhance the development of stem cell research in Indonesia .

Methods Lipoaspirate digested with type I collagenase enzyme then carried filtration .
 Purification of mesenchymal stem cells is done by culturing the cells for 2-3 days followed by disposal of the supernatant .
Confirmation of a homogeneous population of cells with the analysis performed by flowcytometry method in accordance with the criteria of the Mesenchymal and Tissue Stem Cell Committee of the International Society of Cell Therapy .
Results of mesenchymal stem cells that can be obtained using this procedure are as 16.41 ± 8.22 x 108 cells per 120 ml lipoaspirate . Cell culture results showed fibroblastic morphology , in accordance with the characteristics of mesenchymal stem cells and successfully purified from other cells . This was confirmed by flowcytometry analysis showed that CD105 expression , in the absence of expression of HLA – Class II , CD 45 , CD 34 , CD14 , and CD19 .

Conclusion This study showed that mesenchymal stem cells can be isolated from lipoaspirate is simple . This procedure is very possible to be done in a laboratory basis . ( Med J Indones 2009; 18:91-6 )

 

 

Danny Halim, dr. (peneliti Stem Cell Research Working Group-UNPAD, anggota Asosiasi Sel Punca Indonesia (ASPI))
- Harry Murti, S.Si. (peneliti di Stem Cell & Cancer Institute (SCI), anggota ASPI)
- Ferry Sandra, drg, PhD, LFIBA (pendiri SCI, salah satu pendiri ASPI, Direktur SCI & Ketua Dewan Pelaksana ASPI)
- Prof. Arief Boediono, drh, PhD (Guru Besar IPB, peneliti di IPB khususnya bidang partenogenesis, dewan pelaksana ASPI)
- Dr. Tono Djuwantono, dr, SpOG(K) (konsultan fertilitas & endokrinologi reproduksi UNPAD, peneliti di Stem Cell Research Working Group-UNPAD, anggota ASPI)
- Boenjamin Setiawan, dr, PhD (pendiri SCI bersama Ferry Sandra, salah satu pendiri ASPI)

 

 

Terungkapnya sejumlah potensi istimewa stem cell (sel punca) pada akhir abad ke-20 adalah suatu fenomena besar dalam dunia kedokteran. Dengan karakteristik yang dimilikinya, teknologi kedokteran berbasis stem cell menjanjikan harapan kesembuhan total bagi penderita penyakit degeneratif seperti stroke, Alzheimer, diabetes melitus, Parkinson, maupun gagal jantung.

Stem Cell – Dasar Teori & Aplikasi Klinis ini adalah buku yang menyajikan penjelasan ilmiah terpercaya mengenai dasar teori yang menjadi landasan penggunaan stem cell dalam dunia klinis.

 

 

DAFTAR ISI
Bab 1
Definisi dan Biologi Dasar Stem Cell
- Karakteristik Stem Cell
- Jenis-jenis Stem Cell

Bab 2
Keragaman Jenis Stem Cell: Sumber,Teknik Isolasi, Kulturisasi, Diferensiasi, dan Kriopreservasinya
- Stem Cell Embrionik: Sumber & Teknik Isolasinya
- Stem Cell Dewasa: Sumber, Identifikasi, dan Teknik Isolasinya
- Stem Cell Hasil Induksi (induced Pluripotent Stem Cell, iPS)
- Stem Cell Jenis Lain: Stem Cell Fetal dan Stem Cell Kanker
- Kulturisasi dan Diferensiasi Stem Cell secara In Vitro
- Simpan Beku (Kriopreservasi Stem Cell)

 

Bab 3
Mekanisme Stem Cell Dalam Regenerasi
- Homing
- Mekanisme Regenerasi Jaringan oleh Stem Cell
- Penggunaan Stem Cell dalam Terapi Gen Bab 4 Potensi Stem Cell dalam Dunia Riset dan Aplikasi Klinis
- Aging (Penuaan)
- Transplantasi Organ Sebagai Jalan Keluar Penyakit Degeneratif
- Transplantasi Sel Sebagai Harapan Baru Penderita Penyakit Degeneratif
- Peran Stem Cell dalam Terapi Penyakit Degeneratif
- Peran Stem Cell dalam Diagnosis Penyakit Degeneratif

SPESIFIKASI
Tahun Terbit : 2010
Bidang Studi : Kedokteran (Umum, Gigi, Hewan), Biologi, Farmasi
Ukuran Buku : 15,7 x 24 cm
Jumlah Hlm : 160
Warna : Full Color
Kertas : HVS 70 g
Cover : Hardcover
Kode Buku : 0076100030

 

 

 

 

 


ISBN : 978-979-075-330-3

 

 

 

Top of Form

 

 

 

 

 

Application of a modified method for stem cell isolation from lipoaspirates in a basic lab

Caroline T. Sardjono1,2, Melina Setiawan1, Frisca1, Virgi Saputra3, Gwendy Aniko4, Ferry Sandra1

 

 

1 Stem Cell and Cancer Institute

2 Microbiology Department, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia

3 Kalbe Farma Tbk

4 Mitra Keluarga Kemayoran

Abstrak

Tujuan Lipoaspirate mengandung jumlah sel punca mesenkimal yang banyak, sehingga lipoaspirate kini menjadi sumber sel punca mesenkimal yang sangat potensial bagi riset maupun untuk aplikasi klinis. Metode sederhana isolasi sel punca mesenkimal yang dapat diaplikasikan pada laboratorium dasar akan memfasilitasi perkembangan riset sel punca di negara berkembang. Diharapkan, hasil studi ini dapat meningkatkan pengembangan riset sel punca di Indonesia.

 

Metode Lipoaspirate dicerna dengan enzim collagenase type I kemudian dilakukan filtrasi.

Pemurnian sel punca mesenkimal dilakukan dengan mengkultur sel selama 2-3 hari disusul dengan pembuangan supernatan.

Konfirmasi populasi yang homogen dilakukan melalui analisis sel dengan metode flowcytometry sesuai dengan kriteria dari Mesenchymal and Tissue Stem Cell Committee of the International Society of Cell Therapy.

Hasil Sel punca mesenkimal yang dapat diperoleh dengan menggunakan prosedur ini adalah sebanyak 16,41 ± 8,22 x 108 sel per 120 ml lipoaspirate. Sel hasil kultur menunjukan morfologi fibroblastik, sesuai dengan karakteristik sel punca mesenkimal dan berhasil dipurifikasi dari sel lainnya. Hal ini dikonfirmasi dengan analisis flowcytometry yang menunjukan ekpresi CD105, tanpa adanya ekspresi HLA-Class II, CD 45, CD 34, CD14, and CD19.

 

 

Kesimpulan Studi ini menunjukan bahwa sel punca mesenkimal dapat diisolasi dari lipoaspirate secara sederhana. Prosedur ini sangat memungkinkan untuk dilakukan di laboratorium dasar. (Med J Indones 2009; 18:91-6)

Abstract

Aim Lipoaspirate, a wasted by product from liposuction procedure recently has been shown to contain abundant mesenchymal stem cells (MSCs). MSCs have been studied in many research areas to regenerate many cell lineages including, myogenic, cardiomyogenic, and angiogenic lineages. The large quantity of MSCs in lipoaspirate, makes it an attractive source for stem cells used in research and clinical applications. A simplified method which is suitable to be performed in a basic laboratory will facilitate development of stem cell research in developing countries. Therefore the outcomes from this study are expected to encourage the progress of stem cell research in Indonesia.

Methods Lipoaspirate was digested using collagenase type I, followed by a basic filtration method. Purification of MSCs was done by cell culture for 2-3 days followed by supernatant removal. To confirm the homogenous population of MSCs, an analysis using flowcytometry was performed based on the MSCs minimal criteria developed by Mesenchymal and Tissue Stem Cell Committee of the International Society of Cell Therapy.

Resuts MSCs were able to be obtained at 16.41 ± 8.22 x 108 cells per 120 ml lipoaspirate. The cultured cells showed fibroblastic morphology which is characteristic for MSCs and were able to be purified from non-MSCs cells. This was confirmed by flowcytometry assay showing expression of CD105 and the absence of HLA-Class II, CD 45, CD 34, CD14, and CD19.

Conclusions This study has shown that it was feasible to isolate messenchymal stem cell from human lipoaspirate. The procedure was practicable to be performed within a basic laboratory. (Med J Indones 2009; 18: 91-6)

Key words: mesenchymal stem cell, lipoaspirate, stem cell isolation technique

Med J Indones

92

Sardjono et al.

Liposuction is one of the most popular cosmetic surgical procedures worldwide with an estimated one million liposuctions performed annually.1 Lipoaspirate, which often wasted as by product from liposuction procedure recently has been shown to contain abundant mesenchymal stem cells (MSCs).2

The use of lipoaspirate as a source for stem cells offers a far less invasive procedure for cell sampling than the aspiration of bone marrow.

Moreover, the numbers of stem cells obtained from lipoaspirate are reportedly higher in lipoaspirate than its bone marrow counterpart.3

The average of MSCs occurrence in lipoaspirate was 1.2 ± 0.3 per 100 Adipose-derived Cells, much higher compared to 1 MSC per 50,000 bone marrow nucleated cells.4

The clinical utilizations of MSCs from adipose tissue have been reported in the regenerative-reconstructive surgical procedures such as calvarial repair, tracheal repair, fistula healing in Crohn’s disease, osteogenesis imperfecta, breast reconstructions, and tissue reconstruction of post-radiotherapy damage.5-8 Recently, MSC therapies have been extended into treatment for cardiovascular diseases including acute myocardial infarction and chronic heart failure.9

Moreover, several types of medical device have been developed in order to fulfill the high demand of procedures that can cater quick isolation with high yield of MSCs from adipose tissue.6,10

Moreover, there have been several providers offering an option for patients undergo liposuction to be able to store their stem cells in cryopreservation facility.11 This option allows the individuals to take benefits from their own stem cells for future applications.

Mesenchymal stem cells (MSCs), also known as marrow stromal cells or mesenchymal progenitor cells, are defined as self-renewable, multipotent progenitor cells with the capacity to differentiate into several distinct mesenchymal lineages. MSCs can be induced to differentiate into adipogenic, chondrogenic, and osteogenic linages in the laboratory using appropriate cocktails of growth factors and supplements (Figure 1).12

Furthermore, MSCs have been studied in many research area to regenerate cell linages including, myogenic, cardiomyogenic lines, and also differentiate into neurogenic, angiogenic and hepatic lineages.10,13,14 Despite their capability to differentiate in vivo and in vitro into mesenchymal lineages, MSCs have also been shown to have an important role in the maintenance of haematopoiesis.13 and legends Figure 1. Multilineages Differentiation of Mesenchymal Stem Cell (MSC) and additives used to stimulate cell differentiation

ChondrocyteOsteoblastAdipocyteChondrogenicDifferentiation markers-Proteoglycans-Sulfated glycosaminoglycans(stained using SafraninO, Fast Green, or AlcianBlue)OsteogenicEarly markers-Upregulatedalkaline phosphatase(detected by naphtol-based chemical stain)-Late markers-Bone sialoprotein-Osteocalcin-Osteonectin(stained von Kossa, Alizarin Red)AdipogenicDifferentiation markers-Intracellular Lipid vacuoles(stained using Oil Red-O)TGF-􀁅BMP-6High dose dexamethasone1-methyl-3-isobutylxanathineIndomethacinLow dose dexamethasoneL-ascorbic acid 2 phosphate􀁅-glycerophosphateBMP-2, -6, -9MesenchymalStem CellChondrocyteOsteoblastAdipocyteChondrogenicDifferentiation Cell100􀁐m100m

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1. Multitineages differentiation of Mesenchymal Stem Cell (MSC) and additives used to stimulate cell differentiation

93 Vol.18, No.2, April – June 2009 Stem cell isolation from lipoaspirates

Many publications have shown MSCs present and able to be isolated from many tissue types, such as bone marrow, trabecular bone, periosteum, synovial membrane, muscle, dermis, pericytes, blood, and adipose tissue.15-17 These demonstrate the potential of MSCs in addition to their plasticity and their usefulness in cell therapy. It is also of interest that neither autologous nor allogeneic MSCs induce any immunoreacti-vity in the host upon local transplantation or systemic administration.18,19 Finally, the large quantity of MSCs in lipoaspirates, makes it an attractive source for stem cells isolation for research and clinical applications.14,17 An optimized method which is suitable to be performed in a basic research laboratory clearly will facilitate development for basic laboratory to conduct stem cell research. Therefore the aim of this study was to modify the method of Zuk et al so that it would perform well in a minimal laboratory setting.

Methods

Mesenchymal stem cell isolation from lipoaspirates

All protocols were reviewed and approved by the Stem Cell and Cancer Institute Institutional Review Board prior to the study (Proposal number 13/IRB/SCI/KF/2008).

Lipoaspirates were obtained with informed consent from individuals undergoing tumescent liposuction surgery in hospitals collaborated with Stem Cell and Cancer Institute.

Lipoaspirates were stored at 2–8°C for no longer than 24 hours before they were used. Methods used to isolate the mesenchymal stem cells from lipoaspirate were adapted from methods in Zuk et al.17

The raw lipoaspirates (120 ml) were diluted with equal volume of Phosphate Buffer Saline (PBS) and were divided evenly in 50ml-tubes (Figure 2).

The diluted lipoaspirates were centrifuged at 430 × g for 10 minutes continously at 20oC.

After centrifugation, the target cell–containing lipid phase was removed from the top and transferred in to new tubes and diluted with an equal volume of PBS.

 

 

This washing step was repeated twice followed by further an equal volume dilution of cell-containing lipid fraction with pre-warmed (37oC) 0.075% collagenase type I (Sigma) in PBS. Enzyme digestion was done by incubation at 37°C for 30 minutes on an orbital shaker (Figure 3).

After digestion, enzyme activity was neutralized by adding equal volume of Dulbecco’s modified Eagle’s medium (DMEM) containing 10% Fetal Bovine Serum (FBS). Digested product then subjected to centrifugation at 600×g for 10 minutes. Pellet was resuspended in DMEM with 10% PBS then filtered through a 100-

μm strainer mesh attached to a vacuum-pump to remove cellular debris (Figure 4).

Collected cells after filtration were then ready for utilization. An aliquot was taken for cell count using hemocytometer under a light microscope to determined cell yields. Counts and viability were determined with a hemocytometer and the trypan blue dye exclusion technique. Briefly, 10 l trypan blue stock solution (0.4% w/v) was mixed with 10 l cells suspension, incubated for 3 minutes at room temperature then cells were counted in a hemocytometer chamber. With this method, dead cells appear blue and were therefore distinguishable from viable cells.

 

Figure 3. Procedure to isolate mesenchymal stem cells from lipoaspirate using collagenase was done by incubation at 37oC for 30 minutes on a rotating shaker

 

Figure 4. Filtration procedure by using a 100-

m strainer mesh attached to a vacuum pump to remove cellular debris18Figures and legends Figure 1. Multilineages Differentiation of Mesenchymal Stem Cell (MSC) and additives used to stimulate cell differentiation Figure 2. Procedure to dilute lipoaspirate by adding equal volume of Phosphate Buffer Saline (PBS) prior to the washing step

ChondrocyteOsteoblastAdipocyteChondrogenicDifferentiation CellChondrocyteOsteoblastAdipocyteChondrogenicDifferentiation markers-Proteoglycans-Sulfated glycosaminoglycans(stained using SafraninO, Fast Green, or AlcianBlue)OsteogenicEarly markers-Upregulatedalkaline phosphatase(detected by naphtol-based chemical stain)-Late markers-Bone sialoprotein-Osteocalcin-Osteonectin(stained von Kossa, Alizarin Red)AdipogenicDifferentiation markers-Intracellular Lipid vacuoles(stained using Oil Red-O)TGF-􀁅BMP-6High dose dexamethasone1-methyl-3-isobutylxanathineIndomethacinLow dose dexamethasoneL-ascorbic acid 2 phosphate􀁅-glycerophosphateBMP-2, -6, -9MesenchymalStem Cell100􀁐m100m

Figure 3. Procedure to isolate mesenchymal stem cells from lipoaspirate using collagenase was done by incubation at 37 °C for 30 minutes on a rotating shaker Figure 4. Filtration procedure by using a 100-

μm strainer mesh attached to a vacuum-pump to remove cellular debris

Figure 2. Procedure to dilute lipo-aspirate by adding equal volume of Phosphate Buffer Saline (PBS) prior to the washing step

19

 

 

Figure 3. Procedure to isolate mesenchymal stem cells from lipoaspirate using collagenase was done by incubation at 37 °C for 30 minutes on a rotating shaker Figure 4. Filtration procedure by using a 100-

μm strainer mesh attached to a vacuum-pump to remove cellular debris 94 Med J Indones Sardjono et al.

Mesenchymal stem cell culture

The simplest technique to purify MSC from other contaminating cells was done by allowing the cells to adhere on plastic-surfaced disc. Cells were seeded at 1.3x105cells/cm2 in M-199 medium (Gibco 11150) supplemented with 20 % Fetal Bovine Serum (Invitrogen 26140-079), 100 unit/ml penicillin and 0.1 mg/ml streptomycin antibiotics (Sigma P0781), then kept in 37oC, 5% CO2. After 2-3 days unwanted cells (non-MSC cells and debri) were removed by two washes with medium and expanded to reach 80% confluence. In another 6-7 days, adherent cells were detached using 0.25% trypsin EDTA solution (Sigma T4049), then M-199 medium + 20% FBS was used to inactivate trypsin. Detached cells with fibroblast-like morphology were cultured in another flask with cell density of 1.2×105 cells/cm2 for 1 week or until confluence was achieved.

 

Flo

wcytometry assay to determine MSC homogenous population

To confirm the simplified protocols were able to isolate good quality MSCs, several assays were conducted. MSCs have been known to express CD105 and deficient in the expression of HLA Class II, CD34 and CD45.

Expression HLA Class II molecules were determined using PE fluorescein conjugated monoclonal antibodies against HLA Class II (abcam 23901). Antibodies directed against CD45 were conjugated with FITC (BD 555482) and CD34 with FITC (BD 348053) incubated at 4oC in the dark for 15 minutes. Mouse IgG1-FITC (BD 349041) isotype matched negative controls were used to define background staining. The cells then analysed by flow analysis using FACSCalibur 3 argon laser 488nm (Becton Dickinson).

Results

Mesenchymal stem cell isolation and culture

Using the methods described, MSCs were able to be obtained at 16.41 ± 8.22 x 108 cells per 120 ml lipo-aspirate which have provided an abundant number of cells for further used (Table 1). The simplified method has proven to be gentle enough for the cells as shown by the high viability cells obtained (viable cells 92.57% ± 4.5%).

 

 

 

 

 

Table 1. Lipoaspirate donors and cell yield

Donor No.

 

Lipoaspirate volume (ml)

 

Cell yield

 

(x 108)

 

Viability

 

(%)

 

1

 

2

 

3

 

4

 

120

 

120

 

120

 

120

 

4.27

 

20.55

 

22.2

 

18.6

 

90.05

 

91.95

 

89.16

 

99.12

 

average

 

120

 

16.405

 

92.57

 

 

 

 

 

 

Iqbal Rais Stem Cell Patient First in Indonesia
  
TEMPO.CO , Surabaya :
Secretary of the Center for Regenerative Medicine and Stem Cell Hospital Dr . Atopic Dermatitis , Purwati , said Iqbal Rais patient immediately underwent stem cell therapy ( stem cells ) on Wednesday next week .

 Young director , Iqbal Rais , 29 years gush movie trilogy The Tarix Jabrix , lying in hospitals Soetomo weak due to a blood cancer ( leukemia ) .

To Tempo , Purwati said components taken from tissue stem cells bonmero aka spinal cord patients .
Currently , Iqbal was undergoing chemotherapy at the hospital .
” It’s still isolated . Probably , stem cell therapy started next Wednesday , ” said Purwati told Tempo in Jakarta, Friday, 2013 .

Purwati knowledge , Iqbal Rais is the first leukemia patient using stem cell therapy in Indonesia .
 Stem Cell Therapy for leukemia cases abroad , he said , the average success rate of 80 percent .
 Purwati hope , Iqbal body condition is getting better with Stem Cell therapy .
 By injection into a vein Daran , stem cell is inserted into the body Iqbal .
Stem Cell will replace body tissue damaged by the attack cancer cells in blood.

The plan , and the team will Purwati Iqbal menerapi three times Stem Cell therapy . If the patient’s condition indicates a positive development , the use of stem cell therapy to the patient’s body tried really recovered .

Since the first new case of childhood leukemia through stem cell therapy , Purwati reluctant to insure success rate . He hopes stem cell therapy on body Soetomo Hospital Dr Iqbal has a higher success rate than overseas .
 Once therapy , it was USD 25 million charge to the patient . ” It ‘s still a clinical trial . Costs so much, ” he said .

DIANANTA P. Sumedi

Iqbal Rais Pasien Stem Cell Pertama di Indonesia

 

 

 

 

 

 

TEMPO.CO

 

 

 

 , Surabaya

 

:

Sekretaris Pusat Kedokteran Regeneratif dan Stem Cell RSUD Dr. Soetomo, Purwati, mengatakan pasien Iqbal Rais segera menjalani terapi stem cell (sel punca) Rabu,pekan depan.

 

 

 

Sutradara muda, Iqbal Rais, 29 tahun yang membesut film trilogi The Tarix Jabrix, tergolek lemah di RSUD dr Soetomo karena terserang kanker darah (leukemia).

 

 

 

 

Kepada 

Tempo, 

 

Purwati menuturkan komponen stem cell diambilkan dari jaringan bonmero alias sumsum tulang belakang pasien.

Saat ini, Iqbal masih menjalani kemoterapi di rumah sakit tersebut.

 

“Sekarang masih diisolasi. Mungkin, terapi stem cell mulai dilakukan Rabu pekan depan,” kata Purwati kepada Tempo di Surabaya, Jumat 2013.

Sepengetahuan Purwati, Iqbal Rais merupakan pasien leukimia pertama yang menggunakan terapi stem cell di Indonesia.

 

Terapi Stem Cell untuk kasus leukimia di luar negeri, kata dia, tingkat keberhasilannya rata-rata 80 persen.

 

Purwati berharap, kondisi tubuh Iqbal semakin membaik dengan terapi Stem Cell.

 

Melalui injeksi ke pembuluh daran, stem cell dimasukkan ke tubuh Iqbal.

 

Stem Cell akan menggantikan jaringan tubuh yang rusak akibat serangan sel-sel kanker darah.

Rencananya, Purwati dan tim akan menerapi Iqbal sebanyak tiga kali terapi Stem Cell. Bila kondisi badan pasien menunjukkan perkembangan positif, penggunaan terapi Stem Cell dicoba hingga tubuh pasien benar-benar pulih.

 

 

 

Karena baru pertama menangani kasus leukimia melalui terapi Stem Cell, Purwati enggan memastikan tingkat keberhasilannya. Ia berharap terapi Stem Cell RSUD Dr Soetomo pada tubuh Iqbal memiliki tingkat keberhasilan lebih tinggi ketimbang di luar negeri.

 

Sekali terapi, pihaknya mengenakan biaya Rp 25 juta kepada pasien. “Ini kan masih uji klinis. Jadi biayanya segitu,” kata dia.

 

 

 

 

 

 

DIANANTA P. SUMEDI

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Terapi Stem Cell di Jakarta

Stem cell therapy in Jakarta

Mesenchymal stem cell therapy for cartilage defects and fracture reconstruction in RSCM – FKUI
Written by Dr. Okki Ramadian SpPD
Wednesday, January 6, 2010 09:01
Cluster Muscles , Bones and Joints have been preparing for clinical trials ” mesenchymal Stem Cell Therapy for Cartilage Defects and Fracture Reconstruction ” . The principle clinical trial in the case of cartilage is a form of treatment decision marrow from the iliac crest bone patients , cultured bone marrow For isolation and proliferation Bone marrow stromal stem cells ( bMSCs ) or differentiation towards kondrogenesis , and bMSCs implantation in cartilage defect cases , which is symptomatic cartilage defects with an area of ​​more than 4 square meters .
MORE …

  
Biomedical research mesenchyme stem cells
Written by dr Radiana MBiomed
Monday, April 19, 2010 07:57
The development of biomedical research on multipotent stromal mesenchymal cells or more popularly known as mesenchymal stem cells is very fast and lively . Many research lab and biomedical researchers who jumped into the research area and the number is increasing along with the increase in the number of publications and clinical applications of mesenchymal stem cell therapy . This phenomenon on the other hand the negative impact of ambiguity and inconsistency of the results of research in the field of mesenchymal stem cells .
MORE …

  
Regulatory Guide Selpunca India
Written by dr . M. Adi Firman
Wednesday, July 15, 2009 15:01
Each country must have its own guide on the use of stem cells . One of them is India . Here is a guide selpunca regulations in force in India .
For more information , please click on the Stem Cell Regulation in India , the information in the form of pdf files .
You can download these files via the Download Zone menu ( make sure you have registered as a member ) .
  
The role of endothelial progenitor cell ( EPC ) on Neovascularization
Written by dr.Saut Nababan / dr.Okki , SpPD
Wednesday, August 11, 2010 08:10
EPC are cells that have the ability to divide and differentiate into endothelial cells . EPC is part of the stem cells that are more mature and unipoten . Clinically , the EPC can improve conditions of disease that begins with damage to the endothelial cells , both anatomically / structurally and functionally , through the mechanism of neovascularization . The researchers believe that in the bone marrow and peripheral blood flow cells are capable of dividing and differentiate into endothelial cells and ischemic tissue repair due to damage to blood vessel walls . These cells are called endothelial progenitor cells or EPC .
MORE …

  Autologous Stem Cell Transplantation for Autoimmune Disease : Results of a Cohort Study
Written by Dr. Excellency , Dr. Okki SpPD
Wednesday, April 14, 2010 08:48
Autoimmune disease which affects 5-8 % of the population in the world , accounting for short-term morbidity and mortality and long-term meaningful . Although conventional immunosuppressant therapies and new biological agents to control the severe autoimmune disease , this treatment modality is rarely curative . Severe systemic autoimmune diseases such as multiple sclerosis ( MS ) , systemic sclerosis ( SSC ) , rheumatoid arthritis ( RA ) , systemic lupus erythematosus ( SLE ) , juvenile idiopathic arthritis ( JIA ) , hematologic immune cytopenia ( HIC ) , and Crohn’s disease is difficult to treat ; therefore , other treatment strategies are needed . Since 1996 , autologous stem cell transplantation has been performed for the treatment of severe autoimmune diseases refractory to conventional treatment .
MORE …

  
Stem Cell Therapy Regulatory Guide from the FDA
Written by dr . M. Adi Firman
Saturday, July 18, 2009 08:55
Selpunca technological development and adult stem cell based therapy is increasingly prevalent . This prompted the FDA ( Food and Drug Administration ) in 2006 , issued regulations and guidelines on the production and marketing of stem cell -based therapies ( stem – cell – based therapy ) .
Click the following link to listen to the complete guide from the FDA . FDA Regulation of the Stem Cell -Based Therapies .

  

Articles …
• Seminar day : Stem Cell Update ; May 8, 2010
• Clinical Trials Peripheral Blood Stem Cell Implantation in Cardiac Infarction , RSCM – FKUI
• Stem Cell Development Cooperation Iran-FKUI/RSCM
• Stem Cell Clinical Implementation Guide
• Learning from the Dutch Experience Stem Cell Center
• Cooperation Stem Cell Faculty of medicine / RSCM with Leiden Medical Center
• Questions for Materials Posts
• Stem Cell Guide for General
• Stem Cell Therapy in Autoimmune Disease
• Recommendations Cord Blood Storage Services Center of the Royal College of Obstetrics & Gynecology
• Clinical Trials Stem Cell Therapy in Peripheral Arterial Disease type 2 DM
• Presentation Materials Symposium Selpunca
• Prof. Dr. visits . Eduard Willem Fibbe PhD
• Development of Stem Cell Symposium Faculty of medicine / RSCM Success Held

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Latest Articles
• The role of endothelial progenitor cell ( EPC ) on Neovascularization
• Assessing Biomedical mesenchyme stem cells
• Cooperation Stem Cell Faculty of medicine / RSCM with Leiden Medical Center
• Autologous Stem Cell Transplantation for Autoimmune Disease : Results of a Cohort Study
• Seminar day : Stem Cell Update ; May 8, 2010
• mesenchymal stem cell therapy for cartilage defects and fracture reconstruction in RSCM – FKUI
• Clinical Trials Peripheral Blood Stem Cell Implantation in Cardiac Infarction , RSCM – FKUI
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Dahlan Iskan finance therapy ” stemcell ” Putu Wijaya
Friday, November 29, 2013 22:53 pm | 3479 Views
 
SOE Minister Dahlan Iskan ( AFP PHOTOS / Dhoni Setiawan )
Jakarta ( ANTARA News ) – State Enterprises Minister Dahlan Iskan Putu Wijaya help writers who suffered a stroke with pay for treatment through therapy ” stemcell ” .

A press release received by ANTARA here on Friday , said Dahlan was once a colleague Putu Wijaya in the magazine ” Tempo ” Putu visit at his home in Chester district , South Tangerang .

Dahlan come with a medical expert ” stemcell ” from Surabaya , known as the expert ” stemcell ” in Indonesia .

To Putu , Dahlan became a fan of short stories and novels Putu , telling that someone who had a stroke likely to be cured with therapy back ” stemcell ” .

Dahlan as well as introducing new physician home teaching ” stemcell ” in Tokyo and Amsterdam it . ” Thank God , Mas Putu very enthusiastic to join the discussion and states are willing to undergo treatment , ” Dahlan said via text message .

Dahlan said the cost of treatment with the ” stemcell ” it becomes a dependent personality. ” I hope that the Lord to heal us of this great artist , ” said Dahlan .

Putu Wijaya known to have suffered a stroke in early October . As a result of stroke , 69 -year -old artist was not able to work anymore . A number of colleagues and fans then took the initiative to raise funds after reading the news on social media that Putu can not afford the cost of treatment .

Editors : Ruslan Burhani

Terapi sel punca mesenkimal untuk defek tulang rawan dan rekonstruksi fraktur di RSCM-FKUI

 

 

 

Ditulis oleh dr Okki Ramadian SpPD   

 

Rabu, 06 Januari 2010 09:01

 

 

 

 

 

Klaster Otot, Tulang dan Sendi telah mempersiapkan uji klinis “Terapi Sel Punca Mesenkimal untuk Defek Tulang Rawan dan Rekonstruksi Fraktur”.

Prinsip uji klinis pada kasus tulang rawan adalah berupa penanganan yang berupa pengambilan sum-sum tulang dari krista iliaka pasien, kultur bone marrow utk isolasi dan proliferasi Bone marrow stromal stem cells (bMSCs) ataupun diferensiasi kearah kondrogenesis, dan implantasi bMSCs pada kasus defek tulang rawan, yaitu defek tulang rawan simtomatik dengan luas lebih dari 4 meter persegi.

 

 

 

SELENGKAPNYA…

 

 

 

 

 

 

Telaah Biomedik Sel Punca Mesenkim

 

 

 

Ditulis oleh dr Radiana MBiomed   

 

Senin, 19 April 2010 07:57

 

 

 

 

 

Perkembangan riset biomedik terhadap sel mesenkim stroma multipoten atau lebih populer disebut sel punca mesenkim sangat cepat dan semarak. Banyak lab riset dan peneliti biomedik yang terjun ke area riset ini dan jumlahnya meningkat seiring dengan peningkatan jumlah publikasi dan aplikasi klinis terapi sel punca mesenkim. Fenomena ini di sisi lain menimbulkan dampak negatif yakni ambiguitas dan inkonsistensi hasil riset di bidang sel punca mesenkim.

 

SELENGKAPNYA…

 

 

Panduan Regulasi Selpunca India

 

 

 

Ditulis oleh dr. M. Adi Firmansyah   

 

Rabu, 15 Juli 2009 15:01

 

 

 

Setiap negara tentunya memiliki panduan tersendiri mengenai pemanfaatan sel punca. Salah satunya adalah India. Berikut adalah panduan regulasi selpunca yang berlaku di India.

 

Untuk informasi lebih lengkap, silahkan klik 

 

 

Stem Cell Regulation in India

, informasi dalam bentuk file pdf.

Anda dapat mengunduh file ini melalui menu Zona Unduh (pastikan Anda telah terdaftar sebagai member).

 

 

 

 

Peranan Endothelial Progenitor Cell(EPC) pada Neovaskularisasi

 

 

 

Ditulis oleh dr.Saut Nababan/dr.Okki, SpPD   

 

Rabu, 11 Agustus 2010 08:10

 

 

 

 

 

EPC merupakan sel-sel yang memiliki kemampuan untuk membelah dan berdiferensiasi menjadi sel-sel endotel. EPC merupakan bagian dari sel induk yang bersifat lebih matang dan unipoten. Secara klinis, EPC dapat memperbaiki kondisi-kondisi penyakit yang diawali dengan kerusakan sel-sel endotel, baik secara anatomis/struktural maupun fungsional, melalui mekanisme neovaskularisasi. Para peneliti menyakini bahwa di dalam sumsum tulang dan aliran darah tepi terdapat sel-sel yang mampu membelah dan berdiferensiasi menjadi sel-sel endotel dan memperbaiki jaringan iskemik akibat rusaknya dinding pembuluh darah. Sel-sel ini disebut endothelial progenitor cell atau EPC.

 

 

SELENGKAPNYA…

 

 

Transplantasi Autologus Sel Punca untuk Penyakit Autoimun: Hasil Sebuah Studi Cohort

 

 

 

Ditulis oleh dr Mulia , dr Okki SpPD   

 

Rabu, 14 April 2010 08:48

 

 

 

 

Penyakit autoimun yang mana diderita oleh 5-8% penduduk di dunia, menyumbangkan angka morbiditas jangka pendek maupun jangka panjang dan mortalitas yang bermakna. Meskipun terapi imunosupresan konvensional dan agen biologi baru dapat mengontrol penyakit autoimun berat, modalitas pengobatan ini jarang bersifat kuratif. Penyakit autoimun sistemik berat seperti multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immun cytopenia (HIC), dan penyakit Crohn sulit diobati; oleh karena itu, dibutuhkan strategi pengobatan lain. Sejak tahun 1996, transplantasi autologus sel punca telah dilakukan untuk pengobatan penyakit autoimun berat yang refrakter terhadap pengobatan konvensional.

 

SELENGKAPNYA…

 

 

Panduan Regulasi Terapi Sel Punca dari FDA

 

 

 

Ditulis oleh dr. M. Adi Firmansyah   

 

Sabtu, 18 Juli 2009 08:55

 

 

 

Perkembangan teknologi selpunca dan terapi berdasarkan sel punca dewasa ini kian marak. Hal ini mendorong FDA (

Food and Drug Administration) pada tahun 2006, mengeluarkan peraturan dan panduan mengenai terhadap produksi dan pemasaran terapi berbasis sel punca (stem-cell-based therapy). 

Klik pranala berikut untuk menyimak secara lengkap panduan dari FDA tersebut.

 

Regulasi FDA terhadap Terapi Berbasis Sel Punca

.

 

 

 

 

 

 

 

 

Artikel Lain…

 

Seminar sehari : Stem Cell Update; 8 Mei 2010Uji Klinis Implantasi Sel Punca Darah Perifer pada Infark Jantung, RSCM-FKUIKerjasama Pengembangan Sel Punca Iran-FKUI/RSCMPanduan Implementasi Klinis Sel PuncaBelajar dari Pengalaman Pusat Sel Punca BelandaKerjasama Stem Cell FKUI/RSCM dengan Leiden Medical CenterPertanyaan untuk Bahan TulisanPanduan Sel Punca untuk UmumTerapi Sel Punca pada Penyakit AutoimunRekomendasi Jasa Layanan Penyimpanan Darah Tali Pusat dari Royal College of Obstetrics & GynecologyUji Klinis Terapi Sel Punca pada Penyakit Arteri Perifer DM tipe-2Bahan Presentasi Simposium SelpuncaKunjungan Prof Dr. Willem Eduard Fibbe PhDSimposium Pengembangan Sel Punca FKUI/RSCM Sukses Digelar

 

 

 

 

 

 

 

 

 

 

 

 

 

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Dahlan Iskan biayai terapi “stemcell” Putu Wijaya

Jumat, 29 November 2013 22:53 WIB | 3479 Views

 

Menteri BUMN Dahlan Iskan (ANTARA FOTO/Dhoni Setiawan)

Jakarta (ANTARA News) – Menteri BUMN Dahlan Iskan membantu sastrawan Putu Wijaya yang menderita stroke dengan membiayai pengobatan melalui terapi “

stemcell“.

 

Siaran pers yang diterima ANTARA di Jakarta, Jumat, menyebutkan Dahlan yang pernah menjadi teman kerja Putu Wijaya di majalah “Tempo” menjenguk Putu di rumahnya di kawasan Ciputat, Tangerang Selatan.

Dahlan datang bersama seorang dokter ahli “stemcell” dari Surabaya yang dikenal sebagai ahli “stemcell” terbaik di Indonesia.

 

 

Kepada Putu, Dahlan yang menjadi penggemar cerita pendek dan novel Putu, menceritakan bahwa seseorang yang terserang stroke berpeluang disembuhkan kembali dengan terapi “stemcell“.

Dahlan sekaligus memperkenalkan dokter yang baru pulang mengajar “stemcell” di Tokyo dan Amsterdam itu. “Alhamdulillah, Mas Putu sangat antusias mengikuti diskusi dan menyatakan bersedia menjalani perawatan,” kata Dahlan melalui pesan pendek.

Dahlan mengatakan, biaya pengobatan dengan “stemcell” itu menjadi tanggungan pribadinya. “Harapan saya, semoga Tuhan memberikan kesembuhan kepada seniman besar kita ini,” kata Dahlan.

Putu Wijaya diketahui menderita serangan stroke awal Oktober lalu. Akibat stroke, seniman berusia 69 tahun itu tidak bisa berkarya lagi. Sejumlah kolega dan penggemarnya kemudian berinisiatif menggalang dana setelah membaca berita di media sosial bahwa Putu tidak mampu membayar biaya pengobatan.

 

 

Editor: Ruslan Burhani

KOMPAS.com – Many people with kidney failure , heart disease, diabetes , stroke , Parkinson’s cure is now helped by stem cell therapy or stem cell therapy .

Not only degenerative diseases , stem cell therapy can also heal skin problems such as acne , burns , until the problem of aging . Stem cell therapy is also powerful to overcome baldness .

This therapy is the latest medical technology that serves to regenerate cells in the body so it can recover and regrow damaged tissue .

Through two choices therapeutic procedure , ie injection and topical , stem cells derived from humans and processed in the laboratory will be entered into the patient’s body . Implant or implantation of stem cells into the patient’s body is carried out when stem cell processing laboratory results have been developed ( progenitor cells) or differentiated into cells expected .

 Then , stem cells are implanted in the patient’s body will grow and connect with the body’s cells to repair systems and cell regeneration .

” By engineering biology , stem cells can alter other body cells , the damaged bone , skin destroyed , to be normal again , in addition to the cell will continue to improve, “

said stem cell therapy expert , Dr. Indah Julianto , in launching a new breakthrough in stem cell Women’s and Children ‘s Hospital UB , Jakarta , Saturday ( 09/21/2013 ) .

Source of stem cells
Beautiful dr therapy practiced using stem cells from human sources , mainly from umbilical cord blood and umbilical cord Wharton’s jelly . According to Dr. Beautiful , stem cells derived from baby to have the best quality . In applying the therapy , he also uses a source of stem cells from the placenta , not the embryo .

” Immature cells are not known viruses or bacteria . Umbilical cord was never infected with the virus , ” he said .

Dr. Beautiful explains , stem cells derived from the placenta is the source of about 8-10 human stem cells that have been clinically proven through laboratory research . In addition to the placenta , other sources of human stem cells derived from fat , hair , skin , arteries , veins , and others .

Human stem cells , he explained , has 8,000 times the power of its antibiotic and anti – inflammatory . ” Stem cells that miracle . Were no side effects because it is not a drug and not chemicals , ” said Dr. Lovely .

To get optimum benefit from stem cell therapy , stem cells need to be considered quality .

 According to Dr. Beautiful , types of stem cells from the umbilical cord can last only 36 hours .

While stem cells derived from umbilical cord Wharton’s jelly after 48 hours can not function .

” Every 30 minutes , the ability of the cells decreased one percent , ” he said .

Using stem cells that supply is available in UNS Solo , stem cell therapy will take can not be beaten flat .

The duration of therapy depends illness . In patients who experience problems with hair growth , within four months after the treatment , the hair on the head began to grow heavy . Dr. Beautiful using injection and topical procedures to address these issues . As for acne , the treatment is carried out for one month and topically .

However , indeed , for certain diseases , stem cell therapy could take longer.

Dr. Lovely said , people with kidney failure requiring the longest time to undergo this therapy .

” It took about 18 times injection for renal disease , ” he said .

Other diseases that have the potential to improve with stem cell therapy among autism , lupus , epilepsy , blood disorders ( hematopatology ) , autoimmune diseases, multiple sclerosis , Alzheimer’s , and a number of other diseases .

Types of diseases that affect the number of stem cell use ( injection / topical ) will determine how much money is needed for therapy . Per 1 cc of stem cells can cost about Rp 3 million . Once syringes cost about Rp 6 million .

editor :
Asep Candra

KOMPAS.com — Banyak penderita gagal ginjal, jantung, diabetes, stroke, parkinson yang penyembuhannya kini terbantu dengan terapi stem cells atau terapi sel punca.

 

Bukan hanya penyakit degeneratif, terapi sel punca juga dapat menyembuhkan masalah kulit seperti jerawat, luka bakar, hingga masalah penuaan. Terapi sel punca juga ampuh mengatasi kebotakan.

Terapi ini merupakan teknologi kedokteran terkini yang berfungsi meregenerasi sel dalam tubuh sehingga dapat memulihkan dan menumbuhkan kembali jaringan yang rusak.

Lewat dua pilihan prosedur terapi, yakni injeksi dan topikal, sel punca yang bersumber dari manusia dan diproses di laboratorium ini akan masuk ke tubuh pasien. Implan atau penanaman sel punca ke tubuh pasien ini dilakukan bila sel punca hasil pemrosesan di laboratorium sudah berkembang (progenitor cell) atau berdeferensiasi menjadi sel yang diharapkan.

 

Kemudian, sel punca yang ditanamkan di tubuh pasien ini akan berkembang dan berkoneksi dengan sel tubuh untuk melakukan perbaikan sistem dan regenerasi sel.

“Dengan rekayasa biologi, sel punca dapat mengubah sel tubuh lain, tulang yang rusak, kulit hancur, menjadi normal kembali, di samping sel akan terus memperbaiki diri,”

 

ungkap ahli terapi sel punca, dr Indah Julianto, dalam launching terobosan baru sel punca di Rumah Sakit Ibu dan Anak Brawijaya, Jakarta, Sabtu (21/9/2013).

 

 

 

 

 

 

 

Sumber sel punca
Terapi yang dipraktikkan dr Indah menggunakan sumber sel punca dari manusia, utamanya darah dari tali pusat dan jelly wharton tali pusat. Menurut dr Indah, sel punca yang bersumber dari bayi memiliki kualitas terbaik. Dalam mengaplikasikan terapi, ia juga menggunakan sumber sel punca dari plasenta, bukan embrio.

Sel immature tidak kenal virus atau kuman. Tali pusat tidak pernah terinfeksi virus,” ungkapnya.

Dr Indah menjelaskan, sel punca bersumber dari plasenta merupakan satu dari sekitar 8-10 sumber human stem cells yang telah teruji klinis melalui penelitian di laboratorium. Selain plasenta, sumber stem cells manusia lainnya berasal dari lemak, rambut, kulit, arteri, vena, dan lainnya.

Human stem cells, jelasnya, memiliki 8.000 kali kekuatan antibiotiknya dan anti-inflamasi. “Stem cells itu miracle. Tidak ada efek samping karena bukan obat dan bukan bahan kimia,” jelas dr Indah.

Untuk mendapatkan manfaat optimal dari terapi stem cells, kualitas stem cells perlu diperhatikan.

 

 

 

Menurut dr Indah, tipe stem cells dari tali pusat hanya bisa bertahan 36 jam.

 

 

 

Sementara sel punca yang berasal dari jeli wharton tali pusat setelah 48 jam tidak bisa berfungsi.

“Setiap 30 menit, kemampuan sel menurun satu persen,” ungkapnya.

Menggunakan sel punca yang pasokannya tersedia di UNS Solo, terapi stem cells akan memakan waktu yang tak bisa dipukul rata.

 

 

 

 

 

 

 

Durasi terapi ini bergantung penyakit yang diderita. Pada pasien yang mengalami masalah pada pertumbuhan rambut, dalam waktu empat bulan setelah terapi, rambut di kepala mulai tumbuh lebat. Dr Indah menggunakan prosedur injeksi dan topikal untuk mengatasi masalah ini. Sementara untuk mengatasi jerawat, terapi ini cukup dilakukan selama satu bulan dan secara topikal.

Namun, memang, untuk penyakit tertentu, terapi stem cells bisa memakan waktu lebih lama.

 

 

 

 

Dr Indah menyebutkan, penderita gagal ginjal membutuhkan waktu paling lama untuk menjalani terapi ini.

“Butuh sekitar 18 kali injeksi untuk penyakit gagal ginjal,” ungkapnya

 

.

Penyakit lain yang berpotensi membaik dengan terapi sel punca di antaranya autisme, lupus, epilepsi, penyakit gangguan darah (hematopatology), autoimun, multiple sclerosis, alzheimer, dan sejumlah penyakit lainnya.

Jenis penyakit yang memengaruhi jumlah penggunaan sel punca (suntik/topikal) akan menentukan berapa biaya yang dibutuhkan selama terapi. Per 1 cc sel punca biayanya mencapai Rp 3 juta. Sekali suntik biayanya sekitar Rp  6 juta.

 

 

Editor :

 

Asep Candra

 

 

 

 

 

 

SOME disease has been known to be cured by stem cell therapy , such as heart disease , stroke , and even cancer . So how about the stages of treatment of stem cell therapy ?

According to dr . Her Yudi Oktaviono , Sp.JP ( K ) , to process autologous stem cell therapy is that the source is not derived from umbilical cord blood , treatment episodes starting from a thorough examination of the patient’s condition .

” When patients eligible for stem cell therapy , the patient will have blood drawn for her then purified stem cells , ” said dr . Yudi in the seminar ” New Hope Treatment of Disease with Stem Cell Regenerative Therapy through ” in Prodia Tower Auditorium , Central Jakarta , Tuesday ( 03/12/2013 ) .

Furthermore , dr . Yudi explains that the stem cells will be cultivated in the laboratory .
Then , the stem cells are cultivated will continue with the process of cryogenic storage ( low temperature to -196 ° C ) .

” Or it can also be used directly by injection or intravenously its stem cells into the patient’s body , ” he continued .

Meanwhile , in the process of developing stem cell dr . Yudi said that it should also pay attention to sterility and engineering in the work environment . The processing of stem cells , ranging from separation until breeding facilities must be done in accordance with cGMP standards .

For therapeutic purposes , dr . Yudi said that the stem cells will be bred to reach sufficient numbers before being transplanted into the patient .
 In addition , any pengembangbiakannya period varies depending on the type of stem cell that is expected .

” For hematopoietic stem cell takes about 4-5 days , whereas for mesenchymal stem cells reach the incubation period of 4-5 weeks , ” he explained . ( tty )
INILAH.COM , Jakarta – been growing since 1998 , but has yet to bloom or stem cell treatment stem cells in Indonesia .
 Reportedly , no berkembangannya stem cell , because the cost is mahal.d

Beautiful doctor Yulianto Professor of Dermatology Association and the University of March Venerologi admit , in Indonesia the use of stem cells has not been well developed .
 In addition to the lack of regulations , costly problems also be a factor.

” Regulations have not been there , here no one would be examined because it is too difficult and expensive , while they asked him cheap , it’s a hassle , ” said Indah which is also Principal Researcher Dermama Biotechnology Laboratory , at Brawijaya Women & Children Hospital , Jakarta , new – recently.

Stem cell therapy is the latest medical technologies that harness stem cells to regenerate cells in the body so it can recover and regrow body tissue damaged by degenerative diseases .

Beautiful confirms continuing to develop the use of stem cells derived from umbilical cord blood and umbilical cord Wharton’s Jelly with holding four hospitals in Indonesia : Jakarta UB Women Children Hospital , Muwardi RS and RS PKU Muhammadiyah Solo and Mayapada Hospital in Tangerang .

” Because these stem cells is a form of healing that is created directly from the power , I do not want anyone to inhibit this , ” said Belle eagerly .

Beautifully explained , stem cell processing to mnjadi treatment requires lengthy and expensive process . ” Stem cells obtained will be processed in the laboratory and then berdeferensi be expected cell .
It will be an implant or implantation of stem cells into the patient’s body which will further evolve and connect with the body’s cells and perform system repair and regeneration of cells , “said Lovely ..
So far , the disease can be cured with stem cells : the complications of diabetes mellitus , epilepsy , Parkinson’s , heart disease, paralysis , Alzheimer , stroke .
 Stem cells can also treat autism , cerebral palsey and others .
Stem cells also can be used for beauty treatments and skin diseases such as pigmentation , acne and baldness cases . [ aji ]
Many people with kidney failure , heart disease, diabetes , stroke , Parkinson’s cure is now helped by stem cell therapy or stem cell therapy .

Not only degenerative diseases , stem cell therapy can also heal skin problems such as acne , burns , until the problem of aging . Stem cell therapy is also powerful to overcome baldness .

This therapy is the latest medical technology that serves to regenerate cells in the body so it can recover and regrow damaged tissue .

Through two choices therapeutic procedure , ie injection and topical , stem cells derived from humans and processed in the laboratory will be entered into the patient’s body . Implant or implantation of stem cells into the patient’s body is carried out when stem cell processing laboratory results have been developed ( progenitor cells) or differentiated into cells expected .

 Then , stem cells are implanted in the patient’s body will grow and connect with the body’s cells to repair systems and cell regeneration .

” By engineering biology , stem cells can alter other body cells , the damaged bone , skin destroyed , to be normal again , in addition to the cell will continue to improve, “

said stem cell therapy expert , Dr. Indah Julianto , in launching a new breakthrough in stem cell Women’s and Children ‘s Hospital UB , Jakarta , Saturday ( 09/21/2013 ) .

Source of stem cells
Beautiful dr therapy practiced using stem cells from human sources , mainly from umbilical cord blood and umbilical cord Wharton’s jelly . According to Dr. Beautiful , stem cells derived from baby to have the best quality . In applying the therapy , he also uses a source of stem cells from the placenta , not the embryo .

” Immature cells are not known viruses or bacteria . Umbilical cord was never infected with the virus , ” he said .

Dr. Beautiful explains , stem cells derived from the placenta is the source of about 8-10 human stem cells that have been clinically proven through laboratory research . In addition to the placenta , other sources of human stem cells derived from fat , hair , skin , arteries , veins , and others .

Human stem cells , he explained , has 8,000 times the power of its antibiotic and anti – inflammatory . ” Stem cells that miracle . Were no side effects because it is not a drug and not chemicals , ” said Dr. Lovely .

To get optimum benefit from stem cell therapy , stem cells need to be considered quality .

 According to Dr. Beautiful , types of stem cells from the umbilical cord can last only 36 hours .

While stem cells derived from umbilical cord Wharton’s jelly after 48 hours can not function .

” Every 30 minutes , the ability of the cells decreased one percent , ” he said .

Using stem cells that supply is available in UNS Solo , stem cell therapy will take can not be beaten flat .

The duration of therapy depends illness . for certain diseases , stem cell therapy could take longer.

Dr. Lovely said , people with kidney failure requiring the longest time to undergo this therapy . ” It took about 18 times injection for kidney disease , “

 

BEBERAPA penyakit telah diketahui dapat disembuhkan dengan terapi stem cell, seperti penyakit jantung, stroke, bahkan kanker. Lantas bagaimana tahapan pengobatan dari terapi stem cell?

Menurut dr. Yudi Her Oktaviono, Sp.JP(K), untuk proses terapi stem cell secara autologous yang sumbernya bukan berasal dari darah tali pusat, tahapan pengobatan dimulai dari pemeriksaan kondisi pasien secara menyeluruh.

“Apabila pasien memenuhi syarat untuk menjalani terapi stem cell, pasien akan diambil darahnya untuk kemudian stem cell-nya dimurnikan,”jelas dr. Yudi dalam seminar “Harapan Baru Pengobatan Penyakit dengan Stem Cell melalui Terapi Regeneratif” di Auditorium Prodia Tower, Jakarta Pusat, Selasa (3/12/2013).

Selanjutnya, dr. Yudi menjelaskan bahwa stem cell tersebut akan dikembangbiakkan di laboratorium.

Kemudian, stem cell yang dikembangbiakkan tersebut akan dilanjutkan dengan proses penyimpanan kriogenik (suhu rendah sampai -196 °C).

“Atau dapat juga langsung digunakan melalui penyuntikan atau diinfus stem cell-nya ke dalam tubuh pasien,”lanjutnya.

Sementara, dalam proses pengembangan stem cell dr. Yudi mengatakan bahwa itu juga harus memperhatikan kesterilan lingkungan dan teknik dalam bekerja. Proses pengolahan stem cell, mulai dari pemisahan sampai pengembangbiakan harus dilakukan dalam fasilitas yang sesuai dengan standar cGMP.

Untuk keperluan terapi, dr. Yudi mengatakan bahwa stem cell akan dikembangbiakkan hingga mencapai jumlah yang cukup sebelum ditransplantasikan ke tubuh pasien.

Selain itu, masa pengembangbiakannya pun bervariasi tergantung dari jenis stem cell yang diharapkan.

“Untuk stem cell hematopoitik dibutuhkan waktu sekitar 4-5 hari, sedangkan untuk stem cell mesenkimal masa inkubasinya mencapai 4-5 minggu,”terangnya. (tty)

INILAH.COM, Jakarta – Sudah berkembang sejak 1998, namun belum marak pengobatan stem cell atau sel punca di Indonesia.

Kabarnya, tak berkembangannya stem cell, karena biayanya yang mahal.d

 

Dokter Indah Yulianto dari Assosiasi Profesor Dermatologi dan Venerologi Universitas Sebelas Maret mengakui, di Indonesia penggunaan stem cell belum berkembang baik.

Selain belum adanya peraturan, masalah biaya yang mahal juga menjadi faktor penyebab.

“Peraturan belum ada, di sini belum ada yang mau meneliti karena ini terlalu sulit dan mahal, sementara mereka mintanya murah, ini kan repot,” kata Indah yang juga Principal Researcher Laboratorium Bioteknologi Dermama, di Brawijaya Women & Children Hospital, Jakarta, baru-baru ini.

Terapi stem cells merupakan teknologi kedokteran terkini yang memanfaatkan sel punca untuk meregenerasi sel dalam tubuh sehingga dapat memulihkan dan menumbuhkan kembali jaringan sel tubuh yang rusak akibat berbagai penyakit degeneratif.

 

Indah menegaskan terus mengembangkan penggunaan stem cell yang berasal dari darah tali pusat dan Wharton Jelly tali pusat dengan menggandeng empat rumah sakit di Indonesia: Brawijaya Women Children Hospital Jakarta, RS Muwardi dan RS PKU Muhammadiyah Solo dan Rumah Sakit Mayapada Tangerang.

“Karena stem cell ini adalah bentuk penyembuhan yang diciptakan langsung dari yang kuasa, saya tidak mau ada yang menghambat ini,” ujar Indah bersemangat.

Indah menjelaskan, pengolahan stem cell hingga mnjadi pengobatan memerlukan proses panjang dan mahal. “Stem cells yang diperoleh akan diproses di laboratorium kemudian berdeferensi menjadi sel yang diharapkan.

Maka akan dilakukan implan atau penanaman stem cells tersebut ke dalam tubuh pasien yang selanjutnya akan berkembang dan berkoneksi dengan sel-sel tubuh serta melakukan perbaikan sistem dan regenerasi sel,” terang Indah..

Sejauh ini, penyakit bisa sembuh dengan stem cells: diabetes melitus dengan komplikasi, epilepsi, parkinson, jantung, kelumpuhan, alzeimer, stroke.

Stem cell juga bisa mengobati autisme, cerebal palsy dan lainnya.

Stem cell juga bisa untuk perawatan kecantikan dan penyakit kulit seperti pigmentasi, jerawat dan kasus kebotakan. [aji]

Banyak penderita gagal ginjal, jantung, diabetes, stroke, parkinson yang penyembuhannya kini terbantu dengan terapi stem cells atau terapi sel punca.

 

Bukan hanya penyakit degeneratif, terapi sel punca juga dapat menyembuhkan masalah kulit seperti jerawat, luka bakar, hingga masalah penuaan. Terapi sel punca juga ampuh mengatasi kebotakan.

Terapi ini merupakan teknologi kedokteran terkini yang berfungsi meregenerasi sel dalam tubuh sehingga dapat memulihkan dan menumbuhkan kembali jaringan yang rusak.

Lewat dua pilihan prosedur terapi, yakni injeksi dan topikal, sel punca yang bersumber dari manusia dan diproses di laboratorium ini akan masuk ke tubuh pasien. Implan atau penanaman sel punca ke tubuh pasien ini dilakukan bila sel punca hasil pemrosesan di laboratorium sudah berkembang (progenitor cell) atau berdeferensiasi menjadi sel yang diharapkan.

 

Kemudian, sel punca yang ditanamkan di tubuh pasien ini akan berkembang dan berkoneksi dengan sel tubuh untuk melakukan perbaikan sistem dan regenerasi sel.

“Dengan rekayasa biologi, sel punca dapat mengubah sel tubuh lain, tulang yang rusak, kulit hancur, menjadi normal kembali, di samping sel akan terus memperbaiki diri,”

 

ungkap ahli terapi sel punca, dr Indah Julianto, dalam launching terobosan baru sel punca di Rumah Sakit Ibu dan Anak Brawijaya, Jakarta, Sabtu (21/9/2013).

 

 

 

 

 

 

 

Sumber sel punca
Terapi yang dipraktikkan dr Indah menggunakan sumber sel punca dari manusia, utamanya darah dari tali pusat dan jelly wharton tali pusat. Menurut dr Indah, sel punca yang bersumber dari bayi memiliki kualitas terbaik. Dalam mengaplikasikan terapi, ia juga menggunakan sumber sel punca dari plasenta, bukan embrio.

Sel immature tidak kenal virus atau kuman. Tali pusat tidak pernah terinfeksi virus,” ungkapnya.

Dr Indah menjelaskan, sel punca bersumber dari plasenta merupakan satu dari sekitar 8-10 sumber human stem cells yang telah teruji klinis melalui penelitian di laboratorium. Selain plasenta, sumber stem cells manusia lainnya berasal dari lemak, rambut, kulit, arteri, vena, dan lainnya.

Human stem cells, jelasnya, memiliki 8.000 kali kekuatan antibiotiknya dan anti-inflamasi. “Stem cells itu miracle. Tidak ada efek samping karena bukan obat dan bukan bahan kimia,” jelas dr Indah.

Untuk mendapatkan manfaat optimal dari terapi stem cells, kualitas stem cells perlu diperhatikan.

 

 

 

Menurut dr Indah, tipe stem cells dari tali pusat hanya bisa bertahan 36 jam.

 

 

 

Sementara sel punca yang berasal dari jeli wharton tali pusat setelah 48 jam tidak bisa berfungsi.

“Setiap 30 menit, kemampuan sel menurun satu persen,” ungkapnya.

Menggunakan sel punca yang pasokannya tersedia di UNS Solo, terapi stem cells akan memakan waktu yang tak bisa dipukul rata.

Durasi terapi ini bergantung penyakit yang diderita. untuk penyakit tertentu, terapi stem cells bisa memakan waktu lebih lama.

 Dr Indah menyebutkan, penderita gagal ginjal membutuhkan waktu paling lama untuk menjalani terapi ini. “Butuh sekitar 18 kali injeksi untuk penyakit gagal ginjal,”

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