December 27, 2010 by

Time to end stem cell institute CIRM

Wesley J. Smith , San Francisco Chronicle

The California Institute for Regenerative Medicine (CIRM) was created in 2004 as a result of the California Proposition 71, which called for a new bond issue to generate 3 billion dollars in order to support stem cell research in the State. In part, the institute was created as a response to President George W. Bush’s order restricting federal funding of embryonic stem cell research. The hope behind this enormous influx of cash to stem cell research was based on the popular belief that the State would have reduced medical costs, as well as treatments for many of the debilitating diseases that could benefit from stem cell therapy.

According to the author of the article, who is a senior fellow at the Discovery Institute’s Center on Human Exceptionalism and a consultant to the Center for Bioethics and Culture. “The CIRM hasn’t come close to fulfilling those promises. Here’s why California voters should reject the bond issue and shut the agency down in 2014…”

His rationale is that a) CIRM was created primarily to fund human cloning for research and embryonic stem cell research. So far, cloning has failed and embryonic stem cell cures, if they ever come, are a very long way off; b) Questionable uses of taxpayer’s funds. Specifically, $300 million went to help pay for plush research facilities, particularly those associated with board members of CIRM; c) Members of CIRM are paid exorbitant salaries. For example, the head of CIRM makes just under $500,000 a year, Art Torres, a board member and former chairman of the California Democratic Party, works four days a week – for a whopping $225,000 a year.

It is our opinion that basic research is critical for development of new therapies and for advancement of medicine. Therefore, conceptually, there is nothing wrong with supporting the use of taxpayer’s dollars for stem cell research. The issue that we have revolves around what research gets funded and how those projects are in line with the goals for which the funds were donated.

In the “drug development cycle” the first step is basic research and discovery of a biological mechanism of action associated with the disease. The second step is understanding how to manipulate the interaction. The third step is developing an intervention that may theoretically be useful and testing it in animal models of diseases. The fourth step, which is considerably more difficult, is to test the putative therapy in humans either at a low dose in healthy volunteers, or in terminal patients. This usually involves 10-40 patients and is formally called a Phase I clinical trial. Phase II clinical trials are the fifth step of developing a therapeutic. This involves 30-100 patients and assesses efficacy of the therapy in patients with disease. The last step of developing a drug involves conducting Phase III clinical trials, whose aim is to see whether the putative therapy induces therapeutic effects in a double blind, placebo controlled manner.

The majority of research funded by CIRM covers projects that are at the first to third steps, that is, from identifying new biological pathways, to trying to treat mice. Very few CIRM funded projects supported adult stem cell companies that are using their cells to treat patients. We anticipate that with more articles such as the one published by Wesley Smith, CIRM will become more cognizant of the reason why taxpayers supported the Institute: to develop cures faster. Indeed, one can see this increasing support in CIRM for adult stem cell companies in that in October of this year only 5 of 19 grants were for embryonic stem cell research.

Filed Under: News, Stem Cell Research Tagged With: , , , , , ,
December 15, 2010 by

Stem Cell Institute in Panama Collaborates on New Method of Treating Diabetes-Associated Heart Disease

Zhang et al. Journal of Translational Medicine

Diabetes is associated with numerous “secondary complications” including premature heart disease, renal failure, critical limb ischemia (an advanced form of peripheral artery disease) and diabetic retinopathy. One of the common features of these secondary complications is that they are all associated with low levels of circulating endothelial progenitor cells. We have previously discussed the interaction between inflammation and low levels of circulating endothelial progenitor cells http://www.translational-medicine.com/content/7/1/106. It appears that the uncontrolled sugar levels in the blood cause generation of modified proteins, which initiate low level, chronic inflammation. One of the major mechanisms by which sugar- modified proteins induce inflammation is by stimulating a molecular signaling protein called Toll like receptor (TLR)-4. Generally TLR-4 is used by the body to sense “danger”, that is, to sense pathogens, tissue injury, or various factors that may negatively affect the well-being of the host.

In a collaborative study between Stem Cell Institute Panama, Medistem, and the University of Western Ontario, Canada, it was observed that TLR-4 is associated with induction of heart cell (cardiomyocyte) death in diabetic animals. The scientists demonstrated that suppressing the gene encoding for TLR-4 resulted in prevention of heart disease. The results were published in the article Zhang et al. Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4. J Transl Med. 2010 Dec 15;8(1):133. TLR-4 is known to recognize bacterial endotoxin, fragments of degraded extracellular matrix, as well as the stress protein HMBG-1.

In the current experiment, mice were made diabetic by administration of the islet-specific toxin streptozotocin. Diabetic mice were treated with double stranded RNA specific to the gene encoding TLR4. It is known that when cells are treated with double stranded RNA, the gene that is similar to the double strand is silenced. This process is called “RNA interference”.

Seven days after mice became diabetic, as evidenced by hyperglycemia, the level of TLR4 gene in myocardial tissue was significantly elevated. This suggested that not only does hyperglycemia activate TLR4, which was previously known, but that expression of this pro-inflammatory marker actually is increased. Indeed it may be possible that triggers of TLR4 actually act in an autocrine manner in order to increase cell sensitivity

In order to determine whether TLR4 was associated with the cause of cardiomyocyte death, animals were administered the double stranded RNA in order to suppress levels of TLR4. When this was performed the level of cardiomyocyte death was markedly reduced. This is an important finding since usually scientists think of TLR4 as a molecule that activates inflammation through stimulation of the immune

The authors conclude by stating that new evidence is presented suggesting that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.

The research finding that TLR4 is implicated in death of cardiac cells means that agents that suppress it, such as double stranded RNA, may be useful for incorporation into stem cells in order to make the cardiac cells that are derived from the stem cells resistant to death induced by conditions of stress such as hyperglycemia.

Filed Under: Diabetes, Heart Disease, News, Stem Cell Research Tagged With: , , , , , , , ,
December 3, 2010 by

How Inflammation Suppresses Stem Cell Function

Wang et al. PLoS One;5(12):e14206.

Low grade inflammation is well known to correlate with development of numerous disease conditions such as heart failure, kidney failure, and diabetes. It is generally accepted that oxidative stress caused by inflammation is one of the means by which disease evolution occurs. Inflammatory conditions usually generate oxygen free radicals that damage cells and cause the cells of the body to lose function. Importance of reducing inflammation in terms of preventing diseases, such as heart disease, is seen by the beneficial effects of antiinflammatories such as aspirin.

A recent paper (Wang et al. TLR4 Inhibits Mesenchymal Stem Cell (MSC) STAT3 Activation and Thereby Exerts Deleterious Effects on MSC-Mediated Cardioprotection. PLoS One. 2010 Dec 3;5(12):e14206.) suggests that inflammation may actually inhibit the activity of stem cells, and through suppressing the body’s repair processes, causes various diseases to appear.

The mesenchymal stem cell is a type of stem cell found in the bone marrow, fat, heart, and other tissues, that is activated in response to injury and acts to heal damaged tissues. Particularly in the case of heart attacks, it has been demonstrated that administration of bone marrow mesenchymal stem cells causes accelerated healing both in humans and animals. The therapeutic effects of mesenchymal stem cells seem to be mediated by production of growth factors, as well as proteins that support creation of new blood vessels, a process called angiogenesis. Currently several companies are currently developing mesenchymal stem cell based drug candidates including Osiris Therapeutics, Athersys Inc, Mesoblast, and Medistem.

Given the fact that these cells are not a “laboratory experiment” but have actually been used in more than a 1000 patients, understanding conditions that affect their activity, as well as means of making them more effective is important. Inflammatory mediators are believed to influence activity of mesenchymal stem cells, since the protein toll like receptor 4 (TLR4), which recognizes tissue inflammation is found in high concentrations on mesenchymal stem cells. TLR-4 was originally found on cells of the “innate” immune system as a molecule that recognizes “danger signals”.

In order to determine the function of TLR4 on bone marrow mesenchymal stem cells, scientists at Indiana University used mice that have been genetically engineered not to have expression of this protein. Bone marrow mesenchymal stem cells from the mice lacking TLR-4 were demonstrated to function in a similar manner to normal mesenchymal stem cells in the test tube. However when these mesenchymal stem cells were administered to mice after a heart attack, the cells were capable of generating a highly significant improvement in heart function as compared to normal mesenchymal stem cells. The scientists concluded that inflammatory signals “instruct” mesenchymal stem cells to produce less therapeutic factors than they normally would.

These data are very interesting since other reports have suggested that inflammatory mediators actually stimulate mesenchymal stem cells to produce higher amounts of anti-inflammatory factors such as interleukin-10. One of the reasons for the discrepancy may be that inflammation in the context of a heart attack may be different than the inflammatory signals used by other studies.

Filed Under: Adult Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
November 17, 2010 by

Membrane Voltage Changes Control Timing of Stem Cell Differentiation

Researchers at Tufts University have discovered that changes in voltage which naturally occur across adult human stem cell membranes act as a powerful control mechanism which determines the timing of stem cell differentiation.

Led by Dr. Michael Levin, the scientists have shed new light on the role that electrophysiology plays in the differentiation and proliferation of stem cells. According to Dr. Levin, “We have found that voltage changes act as a signal to delay or accelerate the decision of a stem cell to drop out of a stem state and differentiate into a specific cell type. This discovery gives scientists in regenerative medicine a new set of control knobs to use in ongoing efforts to shape the behavior of adult stem cells. In addition, by uncovering a new mechanism by which these cells are controlled in the human body, this research suggests potential future diagnostic applications.”

Using human mesenchymal stem cells (hMSCs), the researchers examined naturally occurring changes in membrane potential (voltage) in the hMSCs, which were harvested from donor bone marrow. As the hMSCs were differentiating into fat and bone cells, the scientists discovered unique voltage patterns that correspond to each stage of the differentiation process. For example, hyperpolarization, in which the difference between the interior and exterior voltages of a cell increases, was found to be characteristic of cells that had already differentiated, but not of cells that still remained undifferentiated. Additionally, the hMSCs were found to exhibit different membrane potentials depending upon whether they were differentiating into bone or fat cells.

When the researchers depolarized the hMSCs by exposing them to high levels of extracellular ions such as potassium, the artificially induced depolarization was found to disrupt the increase in negative voltage that would otherwise naturally occur during differentiation, which resulted in suppressed differentiation as measured by suppressed fat and bone cell differentiation markers. Converseley, when the researchers treated the hMSCs with hyperpolarizing reagents, the various differentiation markers were found to be upregulated.

All cells throughout the human body are, by their very nature, electrical, and terms which are usually reserved for electronics or electrical engineering, such as “current” and “voltage”, are also directly relevant to human physiology. Although biologists do not generally focus much attention on the electrochemistry, nor on the electrophysics, of cellular processes, such electrical phenomena are undeniably at the very essence of organic life. As this study clearly demonstrates, a simple change in voltage across the membrane of a stem cell is all that is required to constitute the “command” that determines whether a stem cell will or will not differentiate.

The Tufts researchers plan to continue further studies to examine in further detail the extent to which hyperpolarization determines the specific types of cells into which a stem cell will differentiate. Ultimately, if scientists could control such electrical processes, cellular differentiation could be used as a therapeutic tool with much greater precision and specificity. Regardless of what, exactly, such future discoveries might reveal, however, the electrodynamics of stem cells is already recognized as playing a vital role in the field of regenerative medicine.

The study was funded in part by the National Science Foundation, the National Institutes of Health, and the U.S. Defense Advanced Research Projects Agency (DARPA). The publication appeared in PLoS ONE, a peer-reviewed, open-access resource of the Public Library of Science.

Filed Under: News, Stem Cell Research Tagged With: , , , , , ,
November 17, 2010 by

Why should mesenchymal stem cells (MSCs) cure autoimmune diseases?

Uccelli A, Prockop DJ. Curr Opin Immunol. 2010 Dec;22(6):768-74. Epub

As many readers of Cellmedicine News most likely realize, the concept of stem cell therapy is still relatively controversial. Despite the fact that clinical trials have demonstrated therapeutic signals that various stem cells are useful in treatment of diseases ranging from multiple sclerosis, to type 1 diabetes, to lupus, people, especially uninformed people in the public media, still treat the field of stem cell therapy of autoimmunity as something “controversial”. This is why we were pleasantly surprised to read the recently published paper of Dr. Darwin Prockop, from Tulane University, which actually used the word “cure” in the title.

In the paper animal and clinical data is reviewed describing effects of a particular type of stem cell, the mesenchymal stem cell, in treatment of autoimmunity. Mesenchymal stem cells were originally found in the bone marrow, and subsequently discovered in other tissues. These cells are capable of generating new tissues, but perhaps more importantly, have been demonstrated to be potent secretors of various growth factors and to modulate the immune system. We discuss some of these points on our youtube channel http://www.youtube.com/watch?v=rEJfGu29Rg8

The paper focuses much attention on multiple sclerosis and the detailed animal experimentation in the mouse model of this disease, experimental allergic encephalomyelitis (EAE), which has provided some detailed clues about how these cells may work. Induction of EAE is typically performed by immunizing mice with peptides or proteins that are found in the myelin. This induces an immune response that attacks the myelin and results in a progressive degeneration of the myelin sheath, as well as loss of function which mimics the human disease. Many of the studies discussed in the paper support the general hypothesis that the mesenchymal stem cells are acting to “reprogram” the immune system in order to stop the immune attack against the myelin but preserve other components of the immune system. The authors then extrapolate how these immunomodulatory mechanisms may have activity against other types of autoimmune conditions.

Currently there are several clinical trials using mesenchymal stem cells for autoimmune conditions. These may be found at www.clinicaltrials.gov if you search the words “stem cells” and “autoimmune.”

Filed Under: Autoimmune Disease, News, Stem Cell Research Tagged With: , , ,
October 14, 2010 by

What Works Better: Stem Cell Mobilization or Stem Cell Administration for Brain Injury

Bakhtiary et al. Iran Biomed J. 2010 Oct;14(4):142-9.

Bone marrow mobilization is used as part of hematopoietic stem cell transplantation in order to collect donor bone marrow stem cells without having to puncture the bone. The process of mobilization is induced by administration of the drug G-CSF, which is approved by the FDA. One interesting question is if instead of giving patients stem cell therapy, if one could simply give G-CSF and have their own stem cells “mobilize” and treated the area of injury. This would be simple and economical as compared to injection of stem cells.

In order to test this, a group from Iran used a rat model of traumatic brain injury and gave either G-CSF or bone marrow derived mesenchymal stem cells.

There were three groups of 10 rats used in the experiments. All rats were subjected to traumatic brain injury by use of a “controlled cortical impact device”. The first group received 2 million bone marrow derived mesenchymal stem cells. The second group received G-CSF to mobilize the bone marrow stem cells. The third group served as a control group. All injections were performed 1 day after injury into the tail veins of rats. The bone marrow derived mesenchymal stem cells were labeled with Brdu before injection into the tail veins of rats. Animals were sacrificed 42 days after TBI and brain sections were stained by Brdu immunohistochemistry.

As compared to controls, both the G-CSF mobilized and the bone marrow mesenchymal stem cell groups had a statistically significant improvement in behavior. When animals were sacrificed at 42 days the observation was made that labeled bone marrow mesenchymal stem cells homed into the area of injury and appeared to contribute to repair.

Although more date is needed when it comes to clinical application, it may be feasible to use G-CSF as part of therapy for traumatic brain injury. One caveat that we find with this is that G-CSF, as its name suggests (granulocyte colony stimulating factor), actually stimulates both increase in granulocyte number and function. While in a controlled laboratory environment brain damage may be relatively “sterile”, in the clinical setting it may be that increased granulocytes may contribute to a higher extent of inflammation and therefore more tissue damage. On the other hand it is possible that mesenchymal stem cells because of their known anti-inflammatory activity may function not only to regenerate the injured brain tissue but also to provide an anti-inflammatory effect.

Filed Under: Adult Stem Cells, Brain Injury, News, Stem Cell Research Tagged With: , , , ,
September 2, 2010 by

Beike Biotechnology Reports on 114 Patients Treated with Novel Cord Blood Stem Cell Protocol

New Approach Opens Door to Expanded Uses of Cord Blood Stem Cells
Beike Biotechnology Press Release

Beiki Biotechnology and Medistem Inc (MEDS.PK) report positive safety data in 114 patients with neurological conditions treated using Beiki’s proprietary cord blood stem cell transplantation protocol. In the peer-reviewed paper “Safety evaluation of allogeneic umbilical cord blood mononuclear cell therapy for degenerative conditions” available at http://www.translational-medicine.com/content/pdf/1479-5876-8-75.pdf ., a team of researchers from Bieke Biotechnology, Medistem Inc, University of Western Ontario, Canada, and University of California, San Diego, describe biochemical, hematological, immunological, and general safety profile of patients with neurological diseases who were observed between 1 month to 4 years after treatment. No serious treatment associated adverse effects were observed. The current report aims to serve as an “expanded Phase I” study, with efficacy data to be published in a subsequent paper.

“Although it is well understood in the scientific community that cord blood stem cells are useful in treatment of terrible degenerative diseases ranging from heart failure, to stroke, to ALS, to multiple sclerosis, the fact that under current protocols immune suppressants are necessary, limits the use of cord blood to treatment of leukemias in the United States and Western Europe.” Said Dr. Hu CEO of Beike . He continued “This is the first time someone has demonstrated on such a large patient population feasibility of non-matched, non-immune suppressed, cord blood stem cell transplantation.”

The current medical dogma states that patients receiving cord blood transplants need to be immune suppressed, otherwise the cord blood will cause a devastating condition termed graft versus host. Due to the potentially lethal effects of immune suppression, cord blood stem cells are not used on a widespread basis, with the exception of treating aggressive leukemias. The technology developed by Beike allows the use of cord blood stem cells without immune suppression, thus opening up the use of this procedure to a much wider patient population.

“It is our honor to collaborate with Beike on this seminal publication. We at Medistem have been developing the concept of “universal donor endometrial regenerative cells”, which are a new stem cell that does not require tissue matching. The fact that Beike has been able to demonstrate safety of transplant by manipulating an established stem cell source is a substantial advancement for the field.” Said Thomas Ichim, CEO of Medistem Inc. “Concretely speaking, the findings of the current paper could open up the use of cord blood for non-hematological diseases, something that to date has not been performed on a wide-spread basis.”

Filed Under: Cord Blood Stem Cells, News, Stem Cell Research Tagged With: , , , , ,
September 1, 2010 by

Scientists identify and isolate adult mammary stem cells in mice

(Times of India) It is well-known that stem cells exist in adult tissues. The most commonly known stem cell, the bone marrow stem cell, plays the physiological role of generating billions of blood cells per hour while being capable of making copies of itself. Subsequent to the discovery of the bone marrow stem cell in the 1960s by Till and McCulloch, other types of stem cells were subsequently identified in other tissues. For example, the brain contains a stem cell compartment term the “dentate gyrus” which is capable of creating new neurons at a basal rate, with acceleration of new neuron formation during pregnancy or after stroke. Other tissue specific stem cells include those found the in liver, the heart, and the spleen. One common characteristic amongst stem cells is their ability to efflux various drugs through expression of the multi-drug resistance (MDR) protein, as well as preferential state of quiescence in absence of growth factor activation.
One important reason to seek tissue-specific stem cells is that if they could be expanded in large numbers they may theoretically be superior to other stem cell types for therapeutic uses. For example, culture-expanded cardiac specific stem cells are superior to bone marrow stem cells at accelerating healing of the heart muscle after a myocardial infarction. These types of stem cells are actually in clinical trials at present.
The other reason for identifying tissue-specific stem cells is that they may be useful in identifying molecular events that occur in the process of normal tissue changing to cancer. This is of interest because cancer stem cells are believed to originate from tissue-specific stem cells acquiring numerous mutations.
Currently researchers from the Fred Hutchinson Cancer Research Center have identified a tissue-specific stem cell in the breast. The scientists developed genetically engineered mice in which the green marker protein GFP was used to identify only breast cells that express the stem cell phenotype. The findings appeared in peer-reviewed journal Genes and Development.
“Until now, we have not been able to identify stem cells in mammary tissue. They have never been detected before with such specificity. It is extraordinary. You can see these green stem cells under the microscope in their pure, natural state,” said Larry Rohrschneider of the Hutchinson Center.
It was demonstrated that the activity of the mammary stem cells is modulated during times associated with breast growth such as puberty and pregnancy.
“We have found that those transplanted green stem cells can generate new mammary tissue and this tissue can produce milk, just like normal mammary epithelial cells,” said co-author Lixia Bai.
“Identification of the exact stem cell and its location is the first critical and fundamental step toward understanding the regulatory mechanisms of these important cells,” she said.
The technology described in the publication may be useful in isolating and expanding human breast specific stem cells. If these studies are reproducible, it will be of great interest to see whether they still possess ability to home to injured tissue, which to date has been clearly demonstrated in bone marrow stem cells but not with too much clarity with cardiac –specific stem cells or other types of tissue-specific stem cells.

Filed Under: Adult Stem Cells, Bone Marrow, News, Stem Cell Research Tagged With: , , ,
August 31, 2010 by

Stem cell therapy benefits patients with chronic heart failure—study

(Neharika Sabharwal) After a heart attack the myocardium (heart muscle) undergoes a period of damage during which cells of the body attempt to heal the injured tissue. This occurs through stem cells found in the heart itself, called cardiac specific stem cells (CSC) as well as bone marrow stem cells which seem to exit the bone marrow, enter circulation, and migrate towards the area of cardiac damage.

Given that the bone marrow stem cells seem to both directly become new heart cells, as well as stimulate formation of new blood vessels that accelerate the healing process, it may be theoretically beneficial to administer bone marrow stem cells to patients after a heart attack. Administration of stem cells is usually performed in these patients by means of a balloon catheter. This device temporarily occludes the artery that is feeding the blood vessel that provides circulation to the area of the injured muscle. While occlusion is occurring cells are administered. This allows the cells to enter the cardiac circulation in a highly concentrated manner. This type of stem cell therapy is termed “post-infarct intracoronary administration of stem cells”.

The use of intracoronary bone marrow transplantation has been published in many clinical trials with overall success in stimulating heart muscle function as judged by the left ventricular ejection fraction. Additionally, bone marrow stem cells have been demonstrated to reduce pathological remodeling by inhibiting the dilation of the ventricles that occurs after a heart attack.

While short-term effects of bone marrow stem cell administration are well-known, little is known about long term effects. A recent study, called the STAR Heart Study, aimed to compare bone marrow cells versus optimal conventional therapy in patients with heart failure due to healed myocardial infarction.

The study demonstrated that intracoronary bone marrow stem cell therapy not only improves ventricular performance and quality of life but also the long term rate of survival in patients with chronic heart failure, claims a new study.

According to researchers, the beneficial effects of stem cell therapy were perceived within three months of the treatment and the effect continued for well over five years. Lead scientist of the study, Bodo-Eckehard Strauer of Duesseldorf’s Heinrich Heine University in Germany said, “Our study suggests that, when administered as an alternative or in addition to conventional therapy, bone marrow cell therapy can improve quality of life, increase ventricular performance and increase survival.”

Currently several companies are developing devices that allow for the use of patient’s own stem cells for intracoronary administration post infarct. One such company is the Hackensack NJ based Amorcyte Inc, which uses standard bone marrow extraction procedures, isolates CD34 positive cells using the Baxter Isolex device, and subsequently infuses the isolated cells using a catheter based technique. The company Aldagen is also performing a similar procedure, however instead of purifying stem cells based on CD34 they are using aldehyde dehydrogenase expression as a means of isolating stem cells from non-stem cells from the bone marrow.

The STAR study was reported at the ‘European Society of Cardiology (ESC) 2010 Congress. It tracked 391 patients with chronic heart failure because of ischemic heart disease following a heart attack. Out of 391 patients, 191 agreed to have the bone marrow stem cell treatment. The remaining 200 who refused therapy participated as the control group.

The patients were monitored for a period of five years after bone-marrow-cell therapy with results at 3 months, one year and five years showing a significant difference between the treatment and control group. At five years only 7 patients who received stem cells died, as compared to 32 in the control group. No treatment associated adverse events of a serious nature were observed.

Dr Mariell Jessup, medical director of the Penn Heart and Vascular Center at the University of Pennsylvania stated, “The hope is that by injecting stem cells into the scarred area, you will bring life back to that area and induce healthy muscle…There’s been ongoing excitement about using stem cells to treat heart disease for some time and this study certainly adds to it.”

Filed Under: Adult Stem Cells, Heart Disease, News, Stem Cell Research Tagged With: , , , ,
August 30, 2010 by

Pluristem to take part in EU stem cell study

(Shiri Habib-Valdhorn, Globes [online], Israel business news) Broadly speaking there are two types of adult stem cell therapies: Those that involve the use of the patient’s own stem cells, called autologous, and those that involve use of another patient’s cells, called allogeneic. There are pros and cons to both approaches.

In the autologous approach the main advantage is that because the cells come from the same patient, there is no issue of immunological rejection or fear of contamination from another person’s infectious agents. The drawbacks with autologous approaches include: a) the fact that stem cell extraction, manipulation, and re-administration requires expensive and laborious procedures, as well as the need for equipment that is not commonly available at most hospitals; b) patients with a variety of disease conditions often have defective stem cells that work suboptimally as compared to stem cells from healthy patients; and c) many times the procedure for extracting the patient’s own stem cells involves painful procedures such as bone marrow aspiration, or potentially dangerous procedures such as stem cell mobilization. This allows the procedure to be performed only for a limited number of times.

The allogeneic stem cell therapy approach has the advantage of using cells that have been generated in large quantities for a specific function and biological activity. This means that the cells used are of a certain quality standard. Additionally, the allogeneic approach does not require complex cell manipulation procedures since the cells are shipped frozen to the point of care. Allogeneic cells can be administered on multiple occasions to the patient if needed. The downside of allogeneic cell therapy is the potential for immunological rejection, as well as patient sensitization. The sensitization of the patient to allogeneic cells may not allow for future use of the stem cells, as well as preclude the patient from bone marrow transplantation.

Pluristem Therapeutics Ltd. (Nasdaq:PSTI; DAX: PJT) is an Israeli company that trades on NASDAQ which is focused on generating allogeneic, “off the shelf” cellular products from placental cells using a proprietary bioreactor device. Originally Pluristem was working on using these stem cells to accelerate bone marrow engraftment after transplantation.

The process of bone marrow transplantation involves administration of chemotherapy and/or radiation to patients with blood malignancies in order to destroy the abnormal cells of the recipient, followed by injection of healthy donor blood making cells (hematopoietic stem cells) in order to provide to the recipient a new immune system. While this procedure has saved thousands of lives, one of the major drawbacks is that the donor cells sometimes take weeks, if not months, to start producing new blood cells. The use of donor cord blood has also been tried in this context experimentally, however, cord blood takes even longer than bone marrow to “engraft” in the recipient. Pluristem believed that its cells produce various growth factors that accelerate the process of engraftment.

In 2009 Pluristem began using its cells for the treatment of critical limb ischemia. This disease is a manifestation of advanced peripheral artery disease characterized by non-ceasing pain, ulcers, and a high rate of amputation. Given that the Pluristem cells produce high amounts of various growth factors, the concept is that administration of these cells into the muscles of patients with critical limb ischemia will result in production of new blood vessels, which will provide increased circulation to the legs of these patients. Other companies such as Medistem Inc are also using allogeneic cells, albeit from different sources (menstrual blood endometrial regenerative cells), for the treatment of this condition.

Recently Pluristem was chosen as one of 19 companies from 12 countries that will participate in a placenta stem cell study financed by EU Seventh Framework Progamme for Research and Development.

The study will be conducted concurrently at 12 European medical centers to examine the effect of placenta stem cell treatments on several kinds of heart cells that are damaged by high blood glucose levels caused by diabetes. The study will examine whether placenta stem cell-based anti-inflammatory agents can prevent or delay the onset of diastolic heart failure (DHF) among diabetics.

This is a new indication for Pluristem’s PLX (PLacental eXpanded) cell therapy product. The company will be allotted $150,000 from the Seventh Framework Progamme for R&D to cover the cost of the research and to develop the stem cells for the program.

Pluristem chairman and CEO Zami Aberman said, “There has been a growing interest in the potential of PLX cells to treat a variety of clinical indications following the release of the PLX-PAD clinical study interim results, which demonstrated safety and shows a trend of efficacy. The decision to use our PLX cells in this DHF study is further verification of the uniqueness of Pluristem’s PLX cells as an off-the-shelf product that requires no tissue matching prior to administration. There is a significant unmet medical need for the treatment of DHF, not only in Europe but also globally, and Pluristem’s placenta-derived cell therapy may provide patients and physicians with an effective and safe treatment option for this disease.”

The use of mesenchymal stem cells for treatment of cardiac diseases has previously been reported by Medistem Inc and Osiris Therapeutics.

Filed Under: News, Stem Cell Research Tagged With: , , , ,
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