July 23, 2009 by

Human Diabetics Treated With Pig Cells

Scientists at the New Zealand company Living Cell Technologies have begun clinical trials today in which cells from newborn pigs will be used for the treatment of Type 1 diabetes. Specifically, the transplanted cells will consist of the beta islet cells from the pancreas, which are the cells that produce insulin. The experimental procedure will be tested on eight human volunteers.

A number of other scientists have expressed concern over the trials, however, pointing out that it’s too early to begin testing on humans since no preclinical animal studies were conducted. Among other risks, scientists caution that any of the numerous viruses that are endemic to pigs could "jump species" and infect the humans, therefore not only causing illness in the 8 volunteers but also potentially triggering a new retroviral pandemic.

The medical director of Living Cell Technologies, Dr. Bob Elliott, however, insists that "there is no evidence of a risk." He describes the piglets that have been selected for the study as having been recovered from 150 years of isolation on islands south of New Zealand, and therefore carry no known infectious agents. It is the unknown infectious agents, however, which have other scientists concerned.

According to Dr. Martin Wilkinson, a past chairman of the New Zealand Bioethics Council, the pig cells pose "a very small risk, low enough to be managed in human recipients. There is no conclusion that it should be banned just because of the possibility of risk." There are many other scientists who disagree, however.

Dr. Elliott has conducted two previous human clinical trials of this nature, the first with 6 patients in New Zealand in 1995 and 1996, and the other with 10 patients in Russia which began in 2007. According to Dr. Elliott, some of the subjects responded with increased insulin production, while in other subjects the implanted cells stopped producing insulin after a year, and there were still other subjects whose bodies rejected the pig cells. None of the human trials were preceded by preclinical animal studies, nor has any scientific paper been published on any of these human trials, although Dr. Elliott says that a paper is scheduled for release by the end of 2009.

Such news represents the opposite extreme of that which most countries face. At the opposite end of the spectrum from the U.S. FDA regulatory regime is a total absence of regulatory oversight. While Phase I, Phase II, and Phase III clinical trials in the U.S. typically require a decade or more of human clinical testing – and must always, without exception, be preceded by successful preclinical trials on animals – the opposite extreme is a country in which preclinical animal trials are not required at all prior to testing on humans. In the first case, patients can grow old and die while waiting around for government approval of a scientifically legitimate clinical therapy; while in the second case, patients can die young as a direct result of the experimental therapy which they have volunteered to receive. Clearly, the issue of exactly how federal government regulatory agencies should adapt their laws to keep pace with medical science is a global problem that is in urgent need of being addressed.

For New Zealand in particular, it seems as though a number of regulatory policy issues remain to be resolved. Previous attempts to form a joint oversight agency with Australia – which would have been known as the Australia New Zealand Therapeutic Products Authority – were indefinitely suspended in July of 2007 when the New Zealand State Services Minister, Annette King, announced at that time that, "The government is not proceeding at this stage with legislation that would have enabled the establishment of a joint agency with Australia to regulate therapeutic products. The (New Zealand) Government does not have the numbers in Parliament to put in place a sensible, acceptable compromise that would satisfy all parties at this time. The Australian Government has been informed of the situation and agrees that suspending negotiations on the joint authority is a sensible course of action."

At the very least, it would seem appropriate to establish some sort of regulatory oversight which requires proof of safety and efficacy in preclinical animal studies before allowing human clinical trials to commence, in which human patients unwittingly become the very first guinea pigs on whom a new and experimental procedure is tested.

Additionally, it would also seem as though the 8 individuals in New Zealand who have volunteered for the experimental pig cell therapy are unaware of other clinical trials which have already been conducted elsewhere throughout the world, and which have utilized adult stem cells from humans, not from animals, in the treatment of human Type 1 diabetes.

For example, it has been demonstrated a number of times that when mesenchymal stem cells (MSCs) are administered to mice whose beta cells have been damaged by the administration of the toxic compound streptozoicin, the MSCs increase insulin production in the mice. The use of adult stem cells to induce islet regeneration is also currently undergoing U.S. FDA-approved clinical trials at the University of Miami. The possibility of stimulating islet regeneration does not necessarily depend on differentiation of the adult stem cells into new islet cells but may also occur through the production of growth factors made by the stem cells and which allow endogenous pancreatic stem cells to start proliferating, thereby healing the injured area. For example, from a mouse study in which chemically-labeled bone marrow-derived MSCs were administered to mice with injured beta cells, the MSCs were actually found to stimulate the islet-activating pancreatic duct stem cell proliferation. The possibility of stimulating endogenous pancreatic duct stem cells by pharmacological means is currently under investigation by the company Novo Nordisk, who has administered a combination of EGF and gastrin to diabetic patients in Phase II clinical trials. However, given that adult stem cells produce a "symphony of growth factors" in addition to gastrin and EGF, the administration of adult stem cells seems to possess a higher possibility of success. Both from the ability of MSCs to differentiate directly into pancreatic cells as well as by their ability to activate endogenous pancreatic stem cells, from preclinical as well as clinical data available throughout the world, there is strong evidence to indicate that MSCs are therapeutic for the restoration of insulin production in the treatment of diabetes.

Furthermore, it is also known that adult stem cell therapy can at least ameliorate and in some cases even reverse the secondary pathologies that are associated with diabetes, such as the variety of complications that result from uncontrolled blood glucose levels such as peripheral vascular disease, neuropathic pain and the dysfunction of various organs such as renal failure. Peripheral vascular disease, for example, is caused by endothelial dysfunction, but it is also known that there is a constant migration of endothelial progenitors from bone marrow sources to the periphery. This migration can be measured through the quantification of the content of endothelial progenitor cells in peripheral blood, and in this manner it has been observed that patients who are diabetic and who have higher levels of circulating endothelial progenitors usually have a lower risk of coronary artery disease. The administration of adult stem cells is also known to rejuvenate old or dysfunctional endothelial cells and to increase responsiveness to vasoactive stimuli. On the other hand, neuropathy, which is a major cause of persistent, chronic pain in diabetic patients, has been reversed in patients who were treated with various adult stem cell populations. This was further documented in highly defined animal models of pain in which bone marrow stem cell administration was found to accelerate nerve healing and to reduce chronic pain. The ability of stem cells to naturally repair injured organs has similarly been described for the heart, the liver and the kidneys. Mechanistically, injured organs transmit elaborate chemical signals, such as SDF-1, which attract stem cells and induce cellular differentiation of the required tissue. Accordingly, based upon evidence such as this, adult stem cell therapy also offers the ideal treatment of secondary complications associated with diabetes.

Additionally, adult stem cells inhibit the mediators that cause insulin resistance. As previously described, one of these mediators which causes the body to resist insulin is known as TNF-alpha (tumor necrosis factor alpha). It has been demonstrated that patients with type II diabetes have abnormally high levels of TNF-alpha, and it is also known that the amount of TNF-alpha in the plasma has been shown to correlate with extensive insulin resistance. In other words, the more TNF alpha that is in a person’s blood plasma, the greater is that person’s insulin resistance. MSCs have been found to shut down TNF-alpha production, thereby shutting off inflammation. A number of studies have documented this fact, one of which was published by Aggarwal et al., in 2005 in the journal Blood, entitled, "Human mesenchymal stem cells modulate allogeneic immune cell response." So there is a great deal of evidence documenting the ability of MSCs to correct the body’s resistance to insulin, with applications to Type I as well as Type II diabetes.

Many studies have also demonstrated that adult stem cells can actually become pancreatic-like stem cells. One such study, conducted by Sun et al., was published in 2007 in the Chin Med J., entitled, "Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro." In this and other similar studies it was demonstrated that stem cells derived from bone marrow can produce insulin in vitro after a "glucose challenge", in which glucose is given to MSCs that have been treated to become similar to pancreatic cells. The results consistently indicate that the MSCs are in fact becoming cells which produce insulin in response to the glucose in vitro, and a number of studies also exist in vivo. One such study was conducted by Lee et al., and published in 2006 in the Proceedings of the National Academies of Science, entitled, "Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice." In this study, the investigators used the streptozoacin toxin to kill the beta cells in the pancreas of mice, and when MSCs were administered to the mice, insulin production was shown to increase. Another study was conducted by Tang et al., and published in the journal Diabetes, entitled, "In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow." In this study, the investigators took stem cells from bone marrow, cultured them, and made cells that appeared to be the beta islet cells. Specifically, the scientists took MSCs, cultured them in glucose and added nicotinamide (the amide part of nicotinic acid, also known as vitamin B3), which is an agent that is known to assist in pancreatic regeneration. The result was the formation of a group of cells that look and behave like pancreatic beta islet cells. The phenotypic expression of these cells does not include CD34 or CD45, therefore these cells are not hematopoietic, but their genotypic expression includes genes that are specific to the pancreas, such as PDX-1, insulin, glucose transporters, etc., so these cells would appear to resemble pancreatic beta islet cells in behavior and function.

Additionally, a group of scientists in Argentina reported in 2007 that 85% of Type II diabetic patients who were treated with their own MSCs were able to stop using insulin. In this technique, stem cells were administered to each patient via a catheter which is directed through the endovascular arteries directly to the pancreatic parenchyma. The catheterization is employed via an arterial route since arteries deliver oxygenated blood to the organs of the body. The catheter is inserted through a puncture in the groin under local anesthesia, and no stitches are required. More than 70 cases of diabetes have been treated according to this technique, with some of these patients having had diabetes for as long as 30 years, and with many of them exhibiting minimal response to conventional treatment. After receiving treatment by this procedure, 90% of these patients have exhibited significant progress which has even led to the complete withdrawal of original medication in these instances. No complications have been seen in any of the patients, even 9 months after treatment. Similar techniques at other laboratories for the treatment of type II diabetes use the patient’s own stem cells which are derived from the patient’s own bone marrow. These bone marrow-derived stem cells are extracted from the patient’s hip and are then separated and expanded in the laboratory, after which time they are injected back into the patient through an arterial catheter in the groin with the use of local anesthesia, as described above.

It is therefore now known that MSCs can correct the two underlying mechanisms of diabetes, namely, the progression of insulin resistance and pancreatic cell death. In regard to the secondary complications, specifically, peripheral neuropathy and neuropathic pain, numerous case reports have documented the neurogenerative abilities of stem cells, and many animal studies have proven that stem cells can prevent neuropathic pain through a direct analgesic effect. One such study was conducted by Klass et al., and published in 2007 in the journal Anesth. Analg., entitled "Intravenous mononuclear marrow cells reverse neuropathic pain from experimental mononeuropathy." Many other clinical reports have also supported the fact that adult stem cells can help regenerate neurons. Similarly, in peripheral artery disease, endothelial dysfunction often results because patients with type II diabetes have low concentrations of circulating endothelial progenitor cells, which are the cells that make new endothelium. Circulating endothelial cells correlate with vascular health, and bone marrow stem cells are rich in endothelial precursor cells. The administration of bone marrow stem cells can therefore improve endothelial health by increasing vascular endothelial function. Another major complication of type II diabetes is kidney failure. This topic was addressed in the same study cited above, conducted by Lee et al., and published in 2006 in the Proceedings of the National Academies of Science, entitled, "Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice." In this study, the mice had been induced to become diabetic through streptozoacin, and the kidneys were examined for inflammatory macrophage infiltration. As with pancreatic tissue, the stem cells were found to home-in on and repair the damaged renal tissue.

Type II diabetes is becoming an increasingly common problem throughout the world, especially in industrialized nations. Although type I diabetes is not as common as type II diabetes, clinical studies have also shown success in treating type I diabetes with adult stem cells. In a study conducted in 2007 by J.C. Voltarelli of Brazil, fourteen patients with type I diabetes were treated with autologous bone marrow stem cells that had been mobilized into the peripheral blood circulation from which they were collected. During follow-up procedures that were conducted between 7 and 36 months, all fourteen of the patients were able to discontinue insulin use.

Adult stem cell therapy has therefore already been described numerous times throughout the medical literature as the first therapy for both type I and type II diabetes which not only alleviates the symptoms of diabetes but also actually reverses the progression of the disease by regenerating damaged tissue and restoring insulin production.

(Please see the related subsection on this website, entitled "Diabetes", listed in the "Research" section).

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
July 23, 2009 by

Mice Created From Skin Cells

In a stunning announcement that has elated some people while horrifying others, two independent teams of researchers in China have announced the creation of mice from reprogrammed stem cells.

Led by Drs. Qi Zhou and Fanyi Zeng of the Chinese Academy of Sciences and Shanghai Jiao Tong University, and Dr. Shaorong Gao at the National Institute of Biological Sciences in Beijing, the separate teams of researchers have each reported the successful creation of mice not from mouse embryos, but from the adult somatic (non-stem cell) skin cells of mice. The skin cells had been reprogrammed to de-differentiate into a more primitive, pluripotent state – known as iPS (induced pluripotent stem) cells – from which entire generations of mice have now been bred.

On the one hand, the announcement offers further evidence for the obsolescence of embryonic stem cell research; but on the other hand, the announcement raises new concerns about cloning and the genetic engineering of embryos. According to Dr. Robert Lanza, CEO of Advanced Cell Technology, "The implications of this are both enormously important and troublesome. It revives many of the issues raised by reproductive cloning."

Both teams of researchers employed basically the same procedure. Using retroviral vectors to deliver 4 genes, the scientists reprogrammed mouse fibroblasts to dedifferentiate into the iPS cells which were then injected into a tetraploid blastocyst – which the scientists created by fusing together 2 cells of a fertilized blastocyst. Tetraploid blastocysts contain twice the normal number of chromosomes, a peculiar feature which renders them incapable of developing normally. Instead of being able to develop into a regular embryo, tetraploids can only develop into extra-embryonic tissue such as the placenta. By choosing to inject the iPS cells into a 2-celled blastocyst, instead of into a normal blastocyst, the researchers could be certain that any resulting embryonic development would be exclusively the result of the iPS cells. Indeed, when each of the tetraploid blastocysts containing the iPS cells was transferred into the uterus of a female surrogate mouse, not only did embryonic development occur, but 20 days later live mice were born.

The first mouse to be born was black, exactly like that from which the original fibroblast had been obtained, and unlike the white mouse from which the tetraploid blastocyst had been formed. DNA tests further confirmed that the mouse – named "Xiao Xiao", or "Tiny" – was the genetic result of the iPS cells.

Dr. Zhou’s team succeeded in creating 37 iPS cell lines, three of which produced 27 live offspring – one of whom was a male who at 7 weeks of age impregnated a female who gave birth to another generation of mice. In total Dr. Zhou and his colleagues have created more than 100 first-generation mice, who in turn have by now given birth to several hundred second-generation mice, all of whom are virtually genetically identical to the original mouse from which the iPS cells had been derived. According to Dr. Zeng, who worked with Dr. Zhou, "This gives us hope for the future therapeutic interventions using patients’ own reprogrammed cells in the future."

The second group of scientists, led by Dr. Gao, created 5 iPS cell lines, one of which produced 4 embryos that survived until birth, although only one of the four lived to adulthood. Nevertheless, Dr. Gao states that such results are "proof that iPS cells are functionally equivalent to embryonic stem cells."

Indeed, this point is the astonishing conclusion of the experiments, namely, that iPS cells and embryonic stem cells are the function equivalent of each other. According to Dr. Konrad Hochedlinger of Harvard University, "This clearly says for the first time that iPS cells pass the most stringent test." As Dr. Robert Blelloch of the University of California at San Francisco adds, "It’s been a lingering concern, why these (iPS) cells couldn’t make animals." But now, he adds, "It’s further evidence that these are not some bizarre cells out there, and that they are very much like normal embryonic stem cells."

Both teams of scientists encountered some abnormalities, however, as indicated by the fact that not all of the embryos survived. According to Dr. Zeng, "We are using the mouse iPS cells to find out the answers to some basic science questions. So far we haven’t detected much tumor growth on a big, global scale. But we still have a lot to do, and a lot of animals to study so we are currently working on looking at the abnormalities in these offspring." Thus far, both teams of scientists collectively have produced more than 200 second-generation offspring and more than 100 third-generation offspring.

Both processes still remain inefficient, however, as Dr. Zhou’s team produced one mouse from 400 blastocysts, while Dr. Zeng’s team produced 22 pups from 1,500 blastocysts. But when Dr. Zeng’s group compared iPS cells that were 14, 20 and 36 days old, she and her colleagues discovered that the greatest number of live pups were born from the iPS cells that were the youngest when they were injected into blastocysts, namely, those iPS cells that were 14 days old. The oldest of Dr. Zeng’s mice is now 9 months old, while Dr. Gao’s are 2 months old.

As exciting and revolutionary as these accomplishments might be, however, the possibility for commercial as well as scientific abuse and exploitation has raised a number of concerns.

As Dr. Lanza adds, "With just a little piece of your skin, or some blood from the hospital, anyone could have your child – even an ex-girlfriend or neighbor, and there’s nothing you could do about it. Any couple could go to an IVF clinic and have a child that is half, say, Albert Einstein or perhaps Brad Pitt or Elizabeth Taylor. This isn’t rocket science. With a little practice, any IVF clinic in the world could probably figure out how to get it to work." As Dr. Lanza further adds, "Genetic modification of the resulting stem cells could be carried out by a scientist tomorrow. For instance, the technology already exists to genetically increase the muscle mass in animals by knocking out a gene known as mystatin, and could be used by a couple who wants a great child athlete."

As Dr. Jonathan D. Moreno, a bioethicist at the University of Pennsylvania, adds, "The culture wars are not over. There was a lot of celebration about the end of the ethical issues with induced pluripotent stem cells. But this is the paradigm case that shows that the old debates are rapidly being transformed into something even more complicated."

The world first learned about iPS cells in 2006 when Dr. Shinya Yamanaka of Kyoto University in Japan announced the successful creation of these cells from mouse skin. Dr. James Thomson in the U.S. then created iPS cells from human skin in 2007, and again from human blood in 2009. Although Dr. Rudolf Jaenisch of the Massachusetts Institute of Technology had tried to create an entire mouse in 2007 using the same laboratory procedure as the scientists in China, he was unsuccessful in getting beyond the late-embryo stage. As he later described, "There were two possible explanations. Either iPS cells aren’t pluripotent so it was impossible, or we just hadn’t tried hard enough. The first would have been more interesting, but I assumed it was the second explanation." Indeed, from these two independent teams of researchers in China, each of whom produced entire generations of mice from a single mouse fibroblast, the world now knows that iPS cells have virtually the same pluripotency and generative potential as embryonic stem cells. As Richard M. Doerflinger of the U.S. Conference of Catholic Bishops points out, "Nobody has been able to find anything that embryonic stem cells can do that these (iPS) cells can’t do. This was the last remaining barrier."

Actually, there is still at least one more barrier – to the newly produced hopes and fears – which remains, and that is the reproducibility of the technique with human cells. In most countries, however, tetraploid experimentation is not allowed with human cells, so a number of questions will have to remain unaswered, at least for awhile.

And there are other technical problems which are already known. Previous studies conducted earlier this month at UCLA indicated that human iPS cells differ significantly from human embryonic stem cells in gene expression, which could have enormous implications for the translatability of iPS experiments from mice to people. According to Dr. Kathrin Plath at UCLA, "iPS cells might do things better or worse than embyronic stem cells. I don’t think we know the answer at this point." Her colleague, Dr. William Lowry, therefore adds that one cannot draw any certain conclusions about human iPS cells from experiments conducted on mouse iPS cells.

The news from China was published online today in two separate journals, Nature and Cell Stem Cell.

Filed Under: News, Stem Cells, Uncategorized Tagged With:
July 22, 2009 by

NeoStem Featured on CBS

The first company to commercialize a method by which healthy adults may bank their own stem cells, NeoStem was the subject this past Sunday of the CBS television feature, "Eye on New York City".

NeoStem has pioneered a process by which endogenous adult stem cells that naturally reside in the bone marrow are "mobilized" to migrate into the peripheral blood, from which they are then collected through a process known as apheresis. Routinely used in other procedures such as the donation of blood platelets, apheresis allows stem cells to be easily separated from the other cells in the blood, so that the non-stem-cell cells may then be returned to the individual after the stem cells are removed. Apheresis is a minimally invasive, painless process that typically lasts approximately 3 to 4 hours, during which time the patient is awake and comfortable – all of which is highly preferable to bone marrow aspiration, the procedure for harvesting adult stem cells from bone marrow but which must be performed under general anesthesia due to the high level of pain that it causes. After the adult stem cells are collected via apheresis, the stem cells are then stored via a cryopreservation method and remain available to the individual indefinitely throughout the future for therapeutic use whenever needed.

According to Dr. Max Gomez, medical expert for CBS, autologous adult stem cells "have become the cutting edge way to treat osteoarthritis of the knee, hip, ankle and even back pain", among other ailments. Additionally, he adds, "The promise appears to be so great that more than 1,000 clinical trials are testing (autologous adult) stem cell therapies for various conditions and showing promising results for heart failure, diabetes, lupus and even macular degeneration", among other conditions.

According to Dr. Robin Smith, CEO of NeoStem, "NeoStem is very focused on autologous adult stem cell therapies being developed for multiple diseases." Among NeoStem’s recent acquisitions is an exclusive license for use of the technology which identifies and isolates VSELs (very small embryonic-like stem cells), which are not actually embryonic stem cells but nevertheless resemble embryonic stem cells in their pluripotency, and which are believed to have a number of potential clinical applications to the treatment of various diseases.

According to the company’s website, "NeoStem is the first company to provide adult stem cell collection and banking services to the general adult population. NeoStem’s medically proven process is a minimally invasive, painless and safe way to collect your adult stem cells. … There are tremendous clinical and economic advantages to autologous stem cell transplantation (receiving your own stem cells) as there are no issues with immune rejection. Engraftment with your own stem cells is faster, safer and much less costly than receiving someone else’s stem cells (allogeneic)." Additionally, as NeoStem points out on their website, "Currently, adult stem cell transplants have been successfully used as the standard of care in treating blood cancers such as leukemia, lymphomas and multiple myelomas. Today, over 2,000 clinical trials are being conducted in the United States looking at treatments for other diseases such as heart disease, diabetes, vascular disease, autoimmune disorders such as lupus, multiple sclerosis, Crohn’s disease, and many more. In addition, adult stem cells are now being used for certain cosmetic procedures and evaluated for further ones."

According to the actress Suzanne Somers, who has utilized NeoStem’s services for banking her own adult stem cells, "Stem cell therapy is the most exciting new breakthrough in medicine. It gives me great peace of mind to know that my own stem cells will be banked as bio-insurance for me. Now I am prepared for my future as the beneficiary of medical benefits while I am alive."

In June of this year, NeoStem signed an exclusive 10-year-long contract with the China-based company Enhance Biomedical Holdings for a collaboration in the development of a network of adult stem cell collection and treatment centers in Taiwan and throughout a number of provinces in China. (Please see the related news articles on this website, entitled "NeoStem Signs Adult Stem Cell Agreemenet in China", dated June 15, 2009, and "NeoStem CEO Invited to Address Medical Tourism at Conference", dated September 8, 2008).

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
July 22, 2009 by

Leading Researcher Joins Cellular Dynamics

Junying Yu, Ph.D., formerly an associate scientist and senior research fellow in Dr. James Thomson’s laboratory at the University of Wisconsin at Madison, has accepted an invitation to join the scientific research staff of Cellular Dynamics International (CDI), the company cofounded by Dr. Thomson.

According to Chris Kendrick-Parker, chief commercial officer at CDI, "Dr. Yu strengthens CDI’s scientific team and our ability to exploit our growing patent portfolio. Junying is one of the top stem cell researchers in the world, and with her on our team we feel confident that we will be able to provide additional, much needed stem cell research tools and therapies to the preclinical, and eventually clinical, market faster."

As Robert Palay, chairman and CEO of CDI, adds, "We are very pleased that, of the many offers Dr. Yu has entertained, she has chosen CDI to further her research and career. Her personal goals align with the company’s goals in being the leader in iPS cell technology, industrializing the process to create the quantity of cells required for use as tools and therapeutics and accelerating the process of bringing personalized medicine to realization."

As Dr. Yu stated, "I’m excited to join the team of scientists at CDI working towards personalized therapeutics. In vitro drug testing can be severely limited by the lack of physiologically relevant models arising from non-human animal models or models that do not appropriately reflect the target population. iPS cell technology overcomes these obstacles and offers the promise of generating differentiated cell types from virtually any genetic background."

Though already distinguished for her collaboration on a number of pioneering breakthroughs, in March of this year Dr. Yu received further recognition for her participation in the development of iPS cells without the use of dangerous viral vectors, a significant achievement which was described in an article published in the journal Science. This new procedure for developing iPS cells – which CDI has termed "iPS 2.0" – brings iPS cell technology one step closer to clinical applications. Prior to this particular breakthrough, Dr. Yu had already garnered attention for her participation in previous stem cell milestones which included the historic announcement in a November 2007 publication in Science in which she and the other members of Dr. James Thomson’s team first described the successful creation of iPS cells from human skin.

According to Dr. Thomson, one of the cofounders and currently the chief scientific officr of CDI, "It has been an absolute privilege to work with Junying for the past six years at UW, and I am excited to continue the relationship. Junying could have gone anywhere, but she chose CDI, an endorsement of which I am proud. I have always been optimistic in CDI’s success, however now I have great confidence. If Junying takes on a project, it succeeds."

Dr. Yu’s appointment to CDI follows a series of other recent announcements by the company that have included two exclusive licensing agreements – one with New York’s Mount Sinai School of Medicine, and the other with IUPUI, the Indiana University-Purdue University Indianapolis – as well as a new scientific breakthrough in which the company announced the first successful creation of iPS cells from normal human blood.

Based in Madison, Wisconsin and co-founded by the renowned embryonic stem cell pioneer Dr. James Thomson along with 3 of his colleagues in 2004, CDI specializes in the development of iPS cells for drug screening. Often referred to as "the father of embryonic stem cell science", James Thomson, VMD, Ph.D., was the first person ever to isolate an embryonic stem cell in the laboratory, first from a nonhuman primate in 1995 and then from a human in 1998. In addition to serving on the Board of Directors and as chief scientific officer of CDI, Dr. Thomson is currently also director of Regenerative Biology at the Morgridge Institute for Research and the John D. MacArthur Professor of Anatomy at the University of Wisconsin at Madison.

As anyone can see, clearly printed at the top of CDI’s website is the phrase, "iPS cells deliver". Contrary to popular opinion, therefore, and despite his distinguished background in embryonic stem cell (ESC) research, Dr. Thomson is no longer focused exclusively on ESCs but instead has turned the focus of his attention to iPS cells, of which he is also a co-discoverer and which he often describes as having a more immediate applicability in medicine than ESCs. Additionally, such an applicability of iPS cells is not so much in the development of actual cell-based therapies as it is in the screening of new pharmaceuticals, as clearly indicated by the commercial direction of CDI’s pipeline. As further described on their website, "Cellular Dynamics is working with scientists worldwide to develop and deploy a number of cell lineages derived from human pluripotent stem cells (hPSCs) as well as a wide range of screening assays and services to aid pharmaceutical development. Currently CDI provides cardiac toxicity drug testing services, including GLP and non-GLP hERG channel electrophysiological assays as well as action potential and cytotoxicity screens using cardiomyocytes. The company is developing additional cell types from iPS cells, including hematopoietic cells (mast and CD34+ cells, megakaryocytes, and red blood cells), hepatocytes, neural cells, adipocytes, and more."

(Please see the related news articles on this website, entitled, "Wisconsin Stem Cell Company Announces Licensing Agreement", dated July 15, 2009; "Cellular Dynamics Creates iPS Cells From Human Blood", dated July 8, 2009; and "Cellular Dynamics and Mount Sinai Sign Licensing Agreement", dated May 29, 2009).

Filed Under: News, Stem Cells, Uncategorized Tagged With:
July 22, 2009 by

Adult Stem Cells Act as Pacemaker

Scientists at the Chiba University Graduate School of Medicine in Japan have announced their discovery of a natural "biological pacemaker" in adult stem cells derived from adipose (fat) tissue. Specifically, the adult stem cells are mesenchymal stem cells (MSCs), and their naturally occurring "pacemaker" qualities may someday be useful in correcting electrical problems in the heart.

According to Dr. Toshinao Takahashi of the Chiba University, "Electronic pacemakers are often used as palliative therapy for people who have conduction problems with the electrical signals that govern the heart beat. However, that therapy has several shortcomings, including possible malfunction and the need for repeated replacement of the device’s power packs and electrodes. Cell therapy could overcome those problems and provide a possible cure for conductive disease. Our goal is to create a biological pacemaker."

The researchers harvested MSCs from the adipose tissue of mice which were then differentiated into beating cells which resembled heart cells in all features including cell surface proteins that serve as cardiac chemical markers. The new cells were then injected into mice who suffered from atrioventricular (AV) block, an electrical signaling problem of the heart which results in an abnormally reduced heart rate. Within a week after treatment with the new cells, the AV block was reversed to some extent, either completely or partially, in half of the mice who received the stem cell transplant.

Adipose tissue is known to be a rich source of MSCs which have been shown in numerous studies to differentiate into a wide variety of tissue types such as bone, muscle, liver, neuron and cardiac cells, among others. As the name implies, MSCs possess qualities of the "mesenchyme" – the unspecialized matrix cells that are found in the early embryo – which is in fact derived from all 3 germ layers, so one would therefore logically expect MSCs to be able to differentiate into most if not all cell and tissue types of the adult human body. Additionally, adipose tissue is known to exhibit a number of unique immunomodulatory properties which would also prove to be especially beneficial in the treatment of a variety of diseases and injuries (as recently reported by N.H. Riordan et al. in a publication in the April 24, 2009 issue of the Journal of Translational Medicine entitled, "Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis").

In the particular treatment of disorders stemming from problems in cardiac electrical conduction and signaling, Dr. Takahashi has concluded that, "Our findings suggest that brown-fat-derived mesenchymal stem cells may become a useful cell source for antiarrhythmic therapy."

The results were presented at the American Heart Association’s Basic Cardiovascular Sciences Conference in Dallas.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , ,
July 21, 2009 by

Adult Stem Cells Restore Memory in Mice

Scientists at the Institute for Memory Impairments and Neurological Disorders at UC-Irvine have used neural stem cells derived from normal, healthy mice to treat other mice that had been genetically engineered to form the neurofibrillary plaques and tangles that characterize Alzheimer’s disease. Just a month after receiving transplantation with the neural stem cells, the diseased mice were found to perform significantly better on memory tests. Further analysis revealed that the neural stem cells alone did not diminish the plaques and tangles in the brains of the mice, nor did the stem cells increase the number of neurons, but instead the stem cells were able to improve cognitive function by strengthening and increasing the number of connections between already existing neurons. The results of this study therefore offer very concrete evidence for the importance of "neural networks" – the brain’s biological circuitry – in cognitive health. A hot topic in the 1990s, neural networks have proven to have a number of applications not only in neuroscience but also in computer engineering fields that include artificial intelligence. Among other things, the large-scale mathematical modelling of synaptic connections and their signaling resulted in the development of highly specialized "learning paradigms" and numerous types of neural network software which continue to have a broad range of applications to machine vision, mapping, virtual reality and any type of adaptive process. Now, a number of studies such as this, which are using stem cells to investigate the various mechanisms of the brain, are shedding further insights into a fundamental neurobiological process which translates readily to a wide variety of modern technological applications.

In the UC-Irvine study, the researchers found that most of the stem cells that were transplanted into the brains of the mice differentiated into astrocytes and oligodendrocytes, as only approximately 6% of the transplanted stem cells actually differentiated into neurons. Most importantly, the transplanted stem cells were found to secrete the protein BDNF (brain-derived neurotrophic factor) which stimulated the growth of neurites – a newly sprouted neuron that can grow into either an axon or a dendrite – thereby strengthening and increasing the number of connections between neurons. Conversely, when the scientists selectively reduced BDNF in the stem cells, the strength and number of the neuronal connections was observed to decrease, as did memory in the mice, thereby offering further evidence for the role of BDNF in maintaining healthy neuronal function and memory. When the scientists injected only the BDNF, without the stem cells, directly into the brains of diseased mice, some cognitive improvement was seen though not as much as when the BDNF was secreted directly by newly transplanted neural stem cells.

According to Dr. Mathew Blurton-Jones of UC-Irvine, the lead author of the study, "If you look at Alzheimer’s, it’s not the plaques and tangles that correlate best with dementia, it’s the loss of synapses – the connections between neurons. The neural stem cells were helping the brain form new synapses and nursing the injured neurons back to health."

As Dr. Frank LaFerla, a coauthor of the study, adds, "Essentially, the cells were producing fertilizer for the brain. This gives us a lot of hope that stem cells or a product from them, such as BDNF, will be a useful treatment for Alzheimer’s."

Alzheimer’s disease is characterized by very specific neurological abnormalities which ultimately result in very specific types of behavioral abnormalities. Neurologically, there are 3 main identifying features of Alzheimer’s disease, namely, 1) beta-amyloid plaques, which form outside and around neurons, 2) neurofibrillary tangles, which form inside dead neurons, and 3) overall dramatic shrinkage of neural tissue. The plaques and tangles in particular have come to be regarded as the hallmarks of Alzheimer’s, although it is not yet known whether these features are a cause of the disease or merely a byproduct of the disease. The gross atrophy of the brain that is seen in advanced stages of Alzheimer’s is a result of the widespread death of neuronal cells, and the concomitant loss of their synaptic connections. In severe cases the brain may be reduced by as much as a third of its normal size. Behaviorally, the symptoms of Alzheimer’s disease are often mistaken in the early stages for a normal part of the aging process. However, Alzheimer’s does not represent normal aging.

The website of the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institutes of Health (NIH), offers the following
definition: "Alzheimer’s disease is a progressive, neurodegenerative disease characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins." Also on the same website, the NINDS researchers further add that, "There is no cure for Alzheimer’s disease and no way to slow the progression of the disease."

Indeed, prior to the advent of stem cell technology, conventional medicine offered no known effective therapy for Alzheimer’s. Now, however, adult stem cell therapy may possibly offer the first type of treatment which not only slows the progression of the disease by eliminating the plaques and tangles, but which also reverses symptoms of the disease by regenerating new neurons.

Approximately 37 million people worldwide suffer from various forms of dementia, with Alzheimer’s disease constituting the majority of cases. It has been estimated that 18 million people throughout the world are afflicted with Alzheimer’s, approximately 5.3 million of whom are in the U.S., and these figures are expected to double by the year 2025. Although Alzheimer’s is often associated with industrialized societies, currently over half of all people who suffer with this disease are reportedly living in developing nations.

In addition to U.S. President Ronald Reagan, many other prominent individuals have suffered from Alzheimer’s disease, including the former Prime Minister of Britain, Harold Wilson, the choreographer George Balanchine, the composer Aaron Copeland, and the actress Rita Hayworth.

(Please see the related sub-section on this website, entitled "Alzheimer’s Disease", listed in the "Research" section).

Filed Under: News, Stem Cells, Uncategorized Tagged With:
July 21, 2009 by

Enrollment Begins in Adult Stem Cell Clinical Trial for Ischemic Stroke

The Canadian company Stem Cell Therapeutics (SCT) has received authorization from the Drug Controller General of India (DCGI) to begin enrollment in the Phase IIb clinical trial for the treatment of acute ischemic stroke with adult stem cells.

The double-blind, randomized, placebo-controlled clinical trial, which has a recruitment target of 128 to 130 patients, will utilize the modified REGENESIS proprietary protocol developed by SCT. Dr. Steven C. Cramer from UC-Irvine and Dr. Michael D. Hill of the University of Calgary are the two principle investigators of the study.

According to Dr. Alan Moore, president and CEO of SCT, "Approval from DCGI to initiate recruitment for the modified REGENESIS stroke trial in India is an exciting milestone for SCT. Jurisdictional approvals have now been granted in India, the U.S. and Canada, therefore we will begin recruiting patients as soon as possible."

In accordance with their regulations, the DCGI states that, "The DCGI approval process categorizes clinical trials into two types. If the study protocol has already been approved by a cognizant regulatory authority in one or more developed countries (such as the U.S., Canada, the U.K., Switzerland, Germany, Australia, Japan, and South Africa), the study is classified as a Type A trial and can be approved using a fast-track process within two to six weeks after the required documentation has been submitted. All other studies are classified as Type B. For these, the approval process is generally 8 to 12 weeks. The Institutional Review Board (IRB) approval process can be conducted in parallel with the DCGI review and, if import licenses are needed, the applications for these can also proceed in parallel. These provisions facilitate the process of getting study protocols in place and quickly initiating the trials." In other words, India is an excellent place in which to conduct clinical trials, since the approval process moves much more quickly than it does in many other countries. A number of businesses from the U.S., the U.K. and Europe are therefore turning to countries such as India for the testing and commercialization of their new medical products, whether related to stem cells or not.

In this particular case, the therapeutic product developed by SCT, known as REGENESIS, contains a proprietary combination of compounds which are designed to stimulate the body’s naturally occurring, endogenous adult stem cells for the healing and repair of damaged tissue. As described on the company’s website, "Stem Cell Therapeutics Corp. is a Canadian public biotechnology company focused on the development and commercialization of drug-based therapies to treat central nervous system diseases. SCT is a leader in the development of therapies that utilize drugs to stimulate a patient’s own resident stem cells. The Company’s programs aim to repair brain and nerve function lost due to disease or injury. The Company’s extensive patent portfolio of owned and licensed intellectual property supports the potential expansion into future clinical programs in numerous neurological diseases such as traumatic brain injury, multiple sclerosis, Huntington’s disease, Alzheimer’s disease, and ALS."

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
July 21, 2009 by

Adult Stem Cells Treat Alzheimer’s in Animals

Researchers at the Burnett School of Biomedical Sciences at the University of Central Florida today announced positive results in the treatment of Alzheimer’s disease with adult stem cells in mice.

Led by Dr. Kiminobu Sugaya, the scientists used a unique combination of neural stem cells differentiated from bone marrow-derived mesenchymal stem cells, together with the compound phenserine – a highly selective AChE (acetylcholinesterase) inhibitor – to treat a mouse model of Alzheimer’s disease. Not only did the scientists observe the regeneration of new neurons in the brains of the mice following the treatment, but they also found a significant reduction in the amyloid plaque that characterizes Alzheimer’s disease.

According to Dr. Sugaya, "If our success with mice can translate into the human brain, it could give hope to patients and their families."

Alzheimer’s disease is characterized by very specific neurological abnormalities which ultimately result in very specific types of behavioral abnormalities. Neurologically, there are 3 main identifying features of Alzheimer’s disease, namely, 1) beta-amyloid plaques, which form outside and around neurons, 2) neurofibrillary tangles, which form inside dead neurons, and 3) overall dramatic shrinkage of neural tissue. The plaques and tangles in particular have come to be regarded as the hallmarks of Alzheimer’s, although it is not yet known whether these features are a cause of the disease or merely a byproduct. The gross atrophy of the brain that is seen in advanced stages of Alzheimer’s is a result of the widespread death of neuronal cells, and the concomitant loss of their synaptic connections. In severe cases the brain may be reduced by as much as a third of its normal size. Behaviorally, the symptoms of Alzheimer’s disease are often mistaken in the early stages for a normal part of the aging process. However, Alzheimer’s does not represent normal aging.

The website of the National Institute of Neurological Disorders and Stroke (NINDS), a branch of the National Institutes of Health (NIH), offers the following official definition: "Alzheimer’s disease is a progressive, neurodegenerative disease characterized in the brain by abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary tangles) composed of misplaced proteins." Also on the same website, the NINDS researchers further add that, "There is no cure for Alzheimer’s disease and no way to slow the progression of the disease."

Indeed, prior to the advent of stem cell technology, conventional medicine offered no known effective therapy for Alzheimer’s. Now, however, adult stem cell therapy may possibly offer the first type of treatment which not only slows the progression of the disease by eliminating the plaques and tangles, but which also reverses symptoms of the disease by regenerating new neurons.

Dr. Sugaya has previously published a number of studies characterizing the physiological function of the beta-amyloid precursor protein, as well as the ability of bone marrow-derived mesenchymal stem cells to differentiate into both neurons and glia. As stated on his webpage, Dr. Sugaya is focused on the ultimate development of a neuroreplacement therapy using human mesenchymal stem cells for the treatment of a number of neurodegenerative diseases which include Alzheimer’s.

Approximately 37 million people worldwide suffer from various forms of dementia, with Alzheimer’s disease constituting the majority of cases. It has been estimated that 18 million people throughout the world are afflicted with Alzheimer’s, approximately 5.3 million of whom are in the U.S., and these figures are expected to double by the year 2025. Although Alzheimer’s is often associated with industrialized societies, currently over half of all people who suffer with this disease are reportedly living in developing nations.

In addition to U.S. President Ronald Reagan, many other prominent individuals have suffered from Alzheimer’s disease, including the former Prime Minister of Britain, Harold Wilson, the choreographer George Balanchine, the composer Aaron Copeland, and the actress Rita Hayworth.

(Please see the related sub-section on this website, entitled "Alzheimer’s Disease", listed in the "Research" section).

Filed Under: News, Stem Cells, Uncategorized Tagged With:
July 20, 2009 by

Cord Blood America Highlights 2009 Stem Cell Progress

Cord Blood America Inc. (CBAI), one of the largest providers in the world of umbilical cord blood stem cell preservation, reviews its accomplishments thus far in 2009. Even though the year is only half over, CBAI considers its achievements thus far in 2009 to be among the most significant in the company’s history. Some of its accomplishments in the first half of this year are described herein.

In January: The company launched its first social media campaign in the industry to start a public conversation about the potential usefulness of adult stem cells and the importance of storing umbilical cord blood. Additionally, the company established its "3 pillars of success" for 2009, which are, namely, organic growth, acquisitions, and debt reduction for an improvement in the company’s balance sheet.

In February: CBAI was listed on the ETF Innovators Stem Cell 40 company index. Additionally, CBAI announced $1 million in long-term debt reduction as part of its cash-flow restructuring.

In March: CBAI was noted as the top stock performer on ETF Innovators Stem Cell index, with a year-to-date stock price increase of 279% at that time.

In April: Congress introduced legislation to promote the "Family Banking of Umbilical Cord Blood" stem cells, which is a major boost to the entire cord blood banking industry. Additionally, CBAI received its first customer in Germany and announced a long-term debt reduction of over $2.5 million.

In May: CBAI announced that it had received $2.3 million for the purpose of building its own stem cell processing and storage laboratory, rather than continuing to outsource the services, which thereby resulted in a further debt reduction of $4.2 million.

In June: CBAI announced further expansion throughout Europe as well as independent contracting with affilates in the Caribbean and Central America.

In July: CBAI has further secured $7.5 in long-term equity financing for acquisition and growth opportunities, while also hiring a separate management team to direct its new stem cell laboratories in the U.S., which will be among the largest in the country, construction on which has already begun.

According to Matthew Schissler, chairman and CEO of CBAI, "On January 6, 2009, the closing CBAI stock price was $0.0017. On July 10, 2009, the closing stock price was $0.0033, a 94% increase in 6 months of trading. That’s not where we want to be, we are still very undervalued, and I understand that the day-to-day swings of our very liquid and volatile stock price cause some investor concern. I tell investors to take a snapshot of the last 6 months, not six hours. Micro cap stocks are perhaps not for the faint-of-heart. We believe we’re building a very valuable company and this snapshot of the past 6 months shows our progress."

Additionally, Mr. Schissler adds, "In January, CBAI stated its mission is to lay the foundation for a much stronger, healthier company by the end of 2009, which included organic growth, acquisition and debt reduction. As you can see by these highlights, we remain laser-focused on executing these strategies. Because of our focus, we are able to raise significant funding to build a lab with the future growth opportunities it affords us. We are also pleased by the current support of stem cell research in Washington, D.C. and Congressional and state legislative focus on family stem cell banking legislation."

CBAI is the parent company of Cord Partners, which was founded in 2002 and became operational on January 1, 2003. According to the company’s website, "Cord Partners, a Cord Blood America company, has established itself as a platinum standard national competitor in the umbilical cord blood storage industry… CBAI was founded on a simple principle: The families who seek stem cell preservation should never have to work to achieve this. By bundling such services as medical kit preparation, medical courier arrangement, 24/7 customer service, easy enrollment, and one price for all services, we feel an unparalleled commitment to our clinets, and have the foundation for providing the highest quality stem cell preservation available."

Umbilical cord blood is an extremely rich source of highly potent adult stem cells, such as mesenchymal stem cells and CD34+ cells, which have already been in use for decades in the clinical treatment of various diseases, safely and without side effects. Unlike embryonic stem cells, adult stem cells derived from umbilical cord blood are ethically noncontroversial, as umbilical cord blood is easily and harmlessly collectable.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
July 20, 2009 by

Engineering Students Demonstrate Sutures Embedded With Adult Stem Cells

Biomedical engineering students at Johns Hopkins University have announced the successful testing of a practical method for delivering adult stem cells to a patient for the treatment of orthopedic and other types of injuries. Specifically, the undergraduate students have constructed and demonstrated a technique by which adult stem cells are embedded into the surgical thread of sutures that are routinely used in procedures to treat injuries such as ruptured tendons.

The team of students consisted of ten udergraduates who were sponsored by the Maryland-based medical technology company Bioactive Surgical Inc., and who consequently won first place for their design in the recent Design Day 2009 competition, conducted annually by the University’s Department of Biomedical Engineering. The sutures contain autologous adult stem cells, and the students have already conducted preclinical trials of the sutures in animal models, although the ultimate goal is translation of the new technology to human medical therapies.

As described on the University’s website, "In collaboration with orthopedic physicians, the students have begun testing the stem cell-bearing sutures in an animal model, paving the way for possible human trials within about five years."

According to Matt Rubashkin, the student team leader, "Using sutures that carry (autologous adult) stem cells to the injury site would not change the way surgeons repair injury, but we believe the stem cells will significantly speed up and improve the healing process. And because the stem cells will come from the patient, there should be no rejection problems."

The students’ corporate sponsor, Bioactive Surgical, developed the concept and then enlisted the student team to assemble and test the prototype during the year-long Design Team course, which is a requisite course in the Department of Biomedical Engineering. Bioactive Surgical will own the rights to the patent, which are currently pending, and a provisional patent application has also been filed which includes the improvements to the design that were made by the ten members of the Johns Hopkins undergraduate team.

In addition to demonstrating the conceptual validity of the prototype in preclinical animal testing with the assistance of orthopedic veterinarians who conducted the surgical procedures, the undergraduate team also performed a number of other related tasks which included preparing grant applications for additional funding of the technology.

Accordeing to Richard Spedden, CEO of Bioactive Surgical, "The students did a phenomenal job." Representatives of Bioactive Surgical envision a medical procedure for humans in which bone marrow would be withdrawn from the hip of a human patient under general anesthesia, from which mesenchymal stem cells would then be isolated and embedded into the novel suture through the patent-pending proprietary process, which would then be used to stitch together the ruptured tendon or other injured tissue.

In conducting their research, the students found that approximately 46,000 people every year in the U.S. alone undergo surgical repair of an Achilles tendon, which costs approximately $40,000 per surgery and can require a year or more of convalescence. As Matt Rubashkin explains, "After surgery, the recovery process can take up to a year. In about 20% of the cases, the surgery fails and another operation is needed. Anything we can do to speed up the healing and lower the failure rate and the additional medical costs could make a big difference."

According to Dr. Lew Schon, a leading foot and ankle surgeon in the greater Baltimore metroplex, one of the inventors of the technology, and an assistant professor of orthopedic surgery at the Johns Hopkins School of Medicine, "These students have demonstrated an amazing amount of initiative and leadership in all aspects of this project, including actually producing the suture and designing the ensuing mechanical, cell-based and animal trials." Additionally, he adds, "The students exceeded all expectations. They have probably cut at least a year off of the development time of this technology, and they are definitely advancing the science in this emerging area."

Grant proposals which the students prepared include further applications of the novel suture technology to other joint injuries such as rotator cuffs, and to non-orthopedic applications such as in cardiology and obstetrics.

In addition to Matt Rubashkin, the other undergraduate members of the team were David Attarzadeh, Raghav Badrinath, Kristie Charoen, Stephanie D’Souza, Hayley Osen, Frank Qin, Avik Som, Steven Su and Lawrence Wei.

Filed Under: News, Stem Cells, Uncategorized Tagged With:
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