The February 9th, 2009 issue of Time Magazine features a cover story entitled, “How the Coming Revolution in Stem Cells Could Save Your Life.” Plastered across the magazine’s front cover is a photograph of a colorful pink and blue blob which is identified as an “induced pluripotent stem cell from an ALS (amyotrophic lateral sclerosis) patient.”

Not surprisingly, this is not the first time that the topic of stem cells has been chosen for the cover of Time Magazine. Among their numerous articles on the subject and its related personalities over the years, Time Magazine also featured a cover story about stem cells in the August 7th, 2006 issue, entitled, “The Truth About Stem Cells: The Hope, The Hype, and What it Means For You”. At that time, plastered across the front cover of the magazine was a microscopic enlargement of a pink and green blob which was identified as an “adult bone marrow stem cell”. The 2006 cover story was ten pages long, 9 pages of which contained text; by comparison, this year’s cover story is only 6 pages long, a mere 5 pages of which contain text. Given the rapid pace of advancements that have transpired in the stem cell field over the past 3 years, one might logically expect a recent article on the topic to be at least as long as, if not even longer than, an article that was written 3 years ago; and perhaps the 2009 article might have been longer than it is, had the author thought to include the topic of adult stem cells. But, for whatever reason, and unlike the 2006 article, the 2009 article is instead devoted exclusively to the topic of everything else but adult stem cells.

In the 2006 article, the reader’s eye was immediately drawn to a two-page illustration of stem cells stretching across pages 42 and 43 of the issue, which is strikingly similar to the two-page illustration that also stretches across pages 42 and 43 of the 2009 issue. As in the 2006 issue, as one might expect, the co-director of Harvard’s Stem Cell Institute, Dr. Douglas Melton, is also extensively interviewed in the 2009 issue. Unlike the 2006 issue, however, the 2009 issue is devoted exclusively to descriptions of research with embryonic stem cells and iPS (induced pluripotent stem) cells, with practically no mention whatsoever of adult stem cells nor of the extraordinary progress that has already been achieved with adult stem cell therapies. In fact, rather than being a scientifically objective presentation of the pros and cons of various types of stem cells, the 2009 article appears to be more along the lines of either a personal biographical tribute to Douglas Melton, or a form of retribution directed against “the dark days of the Bush Administration’s stem-cell restrictions”, or both. But balanced and unbiased, it is not.

Indeed, the 2009 Time Magazine cover story points out, in reference to Dr. Melton’s work, that “Melton’s motivation was, again, both professional and intensely personal,” since this distinguished scientist has two children who suffer from type 1 diabetes: a son who was diagnosed with the disease 17 years ago at the age of 6 months, and a daughter who was also diagnosed with type 1 diabetes 8 years ago at the age of 14. Certainly, no reader would question the relevance nor the importance of personal experiences such as these, which were highly influential in changing the entire direction of Dr. Melton’s career. One does, however, question how it is possible that, in any article which claims to inform readers about a “coming revolution in stem cells” which might “save your life”, the author of the article could systematically avoid all mention of adult stem cell therapies which already exist and which have already been saving lives in clinics around the world. Instead, in an article which purports to inform readers about medical therapies which are so urgently and desperately needed by so many people, not only by Dr. Melton’s children, the author of this article chooses only to feature embryonic stem cells and iPS (induced pluripotent stem) cells, which do not exist at all as therapies. Indeed, the safety and efficacy of embryonic and iPS cells are so questionable that it might be another decade or longer before such cells can be used as clinical therapies, assuming that they can ever be safely and effectively used as clinical therapies at all. And yet, in this article, embryonic stem cells and iPS cells are inaccurately presented as the only possible source of future stem cell therapies for people who are suffering from disease and injury. Perhaps adult stem cells were entirely and mysteriously excluded from this article because adult stem cells do not represent a “coming revolution” but instead represent a current revolution that has already arrived and is already fully upon us and is already taking place at this very moment, in the here-and-now, on a global basis, if anyone would care to notice. By sharp contrast to adult stem cells, however, the therapeutic viability of embryonic stem cells and even of iPS cells is still entirely hypothetical and no one can predict with any certainty when, if ever, embryonic or iPS cells might be available as clinical therapies, but even the most determined of embryonic stem cell experts do not expect embryonic stem cell nor iPS cell therapies to be available in less than a decade.

If there are any dangers that are associated with adult stem cells, or if there had ever been any problems that were ever found with the numerous FDA-approved clinical trials that have already been conducted with adult stem cells, then this would have been the place to highlight and feature such dangers and problems; but instead, the entire topic of adult stem cells is categorically ignored altogether throughout this 2009 Time Magazine cover story. Nowhere to be found at all, adult stem cell therapies are conspicuous by their absence from the whole article. Of course, the numerous clinical applications of adult stem cells have only yielded dramatic successes, not failures, but apparently the purpose of this article was not to inform the public of successful medical breakthroughs that have already occurred. Instead, the purpose of this article seems to have been to inflate public hopes and expectations for future medical breakthroughs that might not ever occur. Oddly enough, however, the author of this 2009 Time Magazine article does acknowledge some, though not all, of the dangers associated with embronic and other types of pluripotent stem cells, as the author clearly states, “Even iPS cells have yet to prove that they are a safe and suitable substitute for the diseased cells they might eventually replace in a patient. Ensuring their safety would require doing away with dangerous genes that can also cause cancer, as well as the retroviral carriers that Yamanaka [the discoverer of iPS cells] originally used.” But nowhere in this article are teratomas ever mentioned, despite the fact that the ability of an embryonic stem cell, and an iPS cell, to form this particularly hideous and dangerous type of tumor is, by definition, one of the requirements by which embryonic and iPS and other types of pluripotent stem cells are identified in laboratories throughout the world. Interestingly, the author makes reference to Geron’s highly publicized upcoming clinical trial with human embryonic stem cells – the first of its kind, and the first ever to attain approval from the U.S. FDA – without actually mentioning the Geron Corporation by name, and also without ever mentioning any of the problems that are inherent in this clinical trial. (Please see the related news article on this website entitled “Geron’s Efforts in Europe are Thwarted”, dated February 13, 2009). Geron’s clinical trial has not even begun patient enrollment yet, and data from the Phase I trial will not even be available until 2011 at the earliest, yet nevertheless this clinical trial was deemed worthy of mention in the article, even though, for whatever reason, the name of the Geron Corporation itself was not; however, nowhere in the article is there any mention whatsoever of any of the adult stem cell companies that have already conducted FDA-approved clinical trials with adult stem cells, such as, most obviously, Osiris Therapeutics, which is already legendary within the scientific community for its pioneering work and repeated, consistent success with its adult stem cell therapies in a number of FDA-approved clinical trials that have already advanced to Phase III. Of course, the fact that Osiris Therapeutics is never mentioned even once in this article would, presumably, have nothing to do with the fact that Osiris Therapeutics is strictly an adult stem cell company, the exclusive focus of which is the development of clinical therapies from adult stem cells, not from embryonic stem cells. Certainly, members of the media would never be biased against adult stem cell companies; instead, we can only give members of the media the benefit of the doubt by magnanimously concluding that they simply don’t understand the scientific and medical differences between these various types of stem cells and stem cell companies, because if they did understand the differences, they would be blowing trumpets from the rooftops of their buildings in excitement over the revolutionary life-saving successes that have already been achieved with adult stem cells.

Some statements within the 2009 Time Magazine article are fundamentally inexplicable, and leave anyone with a true scientific understanding of stem cells scratching his or her head, such as the statement that, “…embryonic stem cells remain the gold standard for any treatments that find their way into the clinic…”, which is a puzzling cliam, to say the least, especially in light of the fact that embryonic stem cells have never advanced to any type of treatment that has ever found its way into the clinic at all. The only type of “gold standard” with which embryonic stem cells are associated is their ability to form the specific type of tumor known as a teratoma, which literally is the “gold standard” by which laboratories around the world identify embryonic and iPS and all other types of pluripotent cells, since the ability to form a teratoma is part of the official scientific definition of pluripotency. Don’t expect to find any mention of teratomas, however, in this article, nor a fairly representative reporting of scientific discoveries and advancements in the stem cell field, since such facts and perspectives are not to be found here. Regarding “treatments that find their way into the clinic”, only adult stem cells, not embryonic stem cells, have ever advanced to the level of actual therapies that have ever found their way into the clinic, yet this fact is never mentioned, not even once, in this entire 2009 Time Magazine article; to the contrary, there seems to be a concerted effort made throughout this article to create the exact opposite, and entirely erroneous, impression.

Of course, the 2006 Time Magazine cover story on stem cells was not without its inaccuracies either. In that issue, in a small side-paragraph entitled “umbilical-cord cells”, under the subheading “Drawbacks”, the author wrote, “An umbilical cord is not very long and doesn’t hold enough cells to treat an adult.” If sentences such as this don’t leave legitimate stem cell scientists cross-eyed and scratching their heads, nothing will, and the most common reaction among scientists that this type of statement most frequently evokes is a simple, “huh?” Apparently, the author of the 2006 Time Magazine cover story had never heard of cell isolation or expansion – even without which, umbilical cord blood is still one of the most plentiful and overly-abundant sources of adult stem cells in the world, being freely and easily accessible everywhere throughout the world, on a daily basis, to such an extent that at any given moment we actually have much more than we could ever possibly use, even if we wanted to treat the entire population of the planet. Even the adult stem cells known as ERCs (endometrial regenerative cells), which are collected in even smaller volumes than umbilical cord blood, are expandable to quantities that outnumber the human population of the planet. Furthermore, given the numerous chemical, molecular and immunological properties of adult stem cells derived from umbilical cord blood, all of which are highly advantageous properties, it is laughable to cite the physical length of an umbilical cord as a “drawback”. But of course, journalists are not usually scientists, and therefore should not be expected to think and reason as scientists do, even though journalists have taken upon themselves the very serious responsibility of reporting scientific news, presumably in an accurate and truthful manner. It could hardly be considered complex science to make the simple observation that children are born every day throughout the entire world, and therefore umbilical cord blood is abundantly available every day throughout the entire world; yet somehow, in an article that was published in 2006 in one of the leading and most trusted magazines in the world, even this simple and obvious fact was lost and obscured by an irrelevant and scientifically false comment.

If anyone really cared about helping the people who suffer from disease and injury and who could benefit from stem cell therapy, and who are in fact in desperate and urgent need of such therapy, would it not seem reasonable at least to mention the FDA-approved clinical trials and actual clinical successes that have already been achieved with adult stem cells? Especially among scientists and journalists, how is it conscienable to completely, categorically, systematically ignore even the mere mention of adult stem cell therapies, when there are numerous people for whom such adult stem cell therapies could literally make the difference between life and death?

At least the 2006 article did mention that adult stem cells “exist in many major tissues, including the blood, skin and brain. They can be coaxed to produce more cells of a specific lineage and do not have to be extracted from embryos.” Strangely, the 2009 article fails to mention even this basic fact. The 2006 article did, despite its other flaws, at least point out that umbilical cords are “useful” because, according to the author, “Although they are primarily made up of blood stem cells, they also contain stem cells that can turn into bone, cartilage, heart muscle and brain and liver tissue. Like adult stem cells, they are harvested without the need for embryos.” By comparison, the 2009 article makes no mention whatsoever of umbilical cord blood at all, nor, in fact, is there any mention whatsoever of adult stem cell therapies, period. There is barely any mention of the fact that there is such a thing as adult stem cells and that they exist at all. In a semantically ambiguous phrasing of words, there is a reference in the 2009 article to stem cells that “can be created from adult cells”, which is stated in a partial sentence that hangs in mid-air next to an illustration of an “egg cell” in which somatic cell nuclear transfer, “genetic transfer” with retroviruses and four genes, and “safer transfer” with “chemicals or safer viruses”, are symbolically depicted. Of course, stem cells that are “created from adult cells” are not the same as “adult stem cells”, since the former (referring to iPS cells and to those other types of cells that are created by somatic cell nuclear transfer, “genetic transfer” and “safer transfer”, whatever exactly that will turn out to be) still pose a number of risks including tumor formation, whereas the latter (adult stem cells) do not pose any such risks, which is precisely why the former do not exist as clinical therapies whereas the latter (adult stem cells) do; but exactly how the non-scientific reader would ever be able to deduce such facts from this article is anyone’s guess. If nothing else, at least the adult stem cells known as mesenchymal stem cells, which are derivable from bone marrow as well as umbilical cord blood, could have been mentioned somewhere in this article, since these cells have already enjoyed a very well documented clinical history for decades. But alas, apparently even mesenchymal stem cells were forbidden from enjoying the right to “equal opportunity” in this article. The mere title of this cover story, “How the Coming Revolution in Stem Cells Could Save Your Life”, might logically imply some mention of the types of stem cells that have already saved lives, and which have already achieved a revolution in medical science; and those types of stem cells are adult, not embryonic, stem cells. Instead, perhaps the cover of this particular issue of Time Magazine could have been more accurately entitled, “How the Dangerous and Problematic Embryonic and iPS Cells Might Never Be Developed into Therapies That Could Save Your Life.”

If nothing else, the most recent, 2009 Time Magazine cover story does manage to offer resounding proof of an explanation for one long-standing mystery, which is, namely, why the general public is usually so confused about stem cells. Without objective and balanced scientific reporting, especially from the most established and respected names in the media, of course the average non-scientific lay person cannot be expected to understand even the most fundamental of scientific facts and principles behind any particular issue. In a few more years, perhaps some time around 2012 or so, maybe Time Magazine might publish yet another cover story about stem cells, by which time perhaps the publishing powers-that-be might not completely and deliberately ignore the increasing number of successes that are being achieved every day with adult stem cells, nor the increasing number of dangers and risks that are inextricably linked to embryonic stem cells and to iPS cells. Perhaps it will take a few more years before it is once again “politically correct” even to mention the topic of adult stem cell therapies, and thereby to publish a scientifically objective article about a critically important scientific field. The very same people who accuse the previous Administration of using politics and ideology instead of science to dictate policy, are in fact now guilty themselves of the very same thing, as they attempt to impose their own personal biases and prejudices upon others through the exact same fatally flawed approach. Hopefully, at some time in the future, perhaps both sides of the great political and ethical divide might be able to agree upon the same scientific facts; but how many people will die in the next few years, as they patiently wait for the media to get around to reporting accurately and truthfully about medical therapies with adult stem cells that already exist and are already available?

One thing is certain, though, as Dr. David Scadden, co-director of the Harvard Stem Cell Institute, is quoted as saying in the 2009 Time Magazine article: “It’s a wonderful time [for the stem-cell field]. Keep your seat belt on, because this ride is going to be wild.” At the very least, no one can argue with that claim.

In a controversial landmark decision, the U.S. Food and Drug Administration (FDA) has granted approval to the California-based biotech company Geron to commence the first human clinical trials ever to be conducted with embryonic stem cells. The trials, which are scheduled to begin in the summer of 2009 at 7 participating medical centers, will consist of administering embryonic stem cells in 8 to 10 paraplegic parients at the site of injury as soon as possible after an injury but no later than 2 weeks following an injury, before scar tissue has had time to develop. The objective of Phase I of the trials, which will be limited to patients with injuries in the middle of the spine, will be to evaluate safety. Evaluations of efficacy, in the form of patient improvement, will come later. Participating patients will also receive immunosuppressive drugs for the first couple of months in order to help minimize the risk of immune rejection. Follow-up will last for at least one year.

According to Dr. Thomas B. Okarma, Geron’s president and CEO, “This approach is one that reaches beyond pills and scalpels to achieve a new level of healing.” Nevertheless, the procedure comes with a disclaimer, since the treatment is neither expected to be a total nor an immediate cure, nor are patients expected to experience a significant restoration of function. As Dr. Okarma explains, “Any return of bladder or bowel function, a return of sensation, or a return of lower extremity locomotion would be a very exciting finding.”

Similarly, Peter Kiernan, chairman of the Christopher And Dana Reeve Foundation, is hopeful but cautious not to inflate expectations unrealistically. As he explained, “Of the millions of people dealing with paralysis in our nation, they are all delighted with subtle increases in function. We eat, drink, sleep getting people out of wheelchairs, but the reality of the world we are in is if people get bowel function, some sexual function, some ability for movement, that’s a wonderful outcome.”

The embryonic stem cells that will be used in Geron’s clinical trials were obtained from one of the already existing embryonic stem cell lines that former President Bush had approved for research, and is unrelated to President Obama’s promises of policy changes, which have yet to occur.

However, a number of million-dollar questions still remain unanswered, especially those related to whether or not immunosuppressive drugs will be enough to prevent an immune rejection of the stem cells, and whether or not these embryonic stem cells will cause teratomas in the patients. Time will tell.

The ability of embryonic stem cells to form the specific type of tumor known as a teratoma is the universal laboratory test by which embryonic stem cells are identified, since the ability to form a teratoma is, by definition, the measure of pluripotency. In stem cell laboratories throughout the world, if a cell is able to form a teratoma, then it is recognized as being an embryonic stem cell or some other type of pluripotent stem cell, but if it is not able to form a teratoma then it is recognized as being some other type of cell which is not embryonic and which lacks pluripotency. It is precisely for inherent medical risks such as teratomas that embryonic stem cells had not received previous FDA authorization to be used in clinical trials in the U.S., prior to Geron. Since adult stem cells are not pluripotent but instead are multipotent, they do not pose the risk of teratoma formation which is why adult stem cells are already being used in clinics around the world to treat patients with a wide variety of diseases and injuries. By sharp contrast, scientists agree that any hope of a safe and effective clinical therapy being developed from embryonic stem cells is still at least another decade away, if not further.

The cost of the therapy also remains an unknown factor, as well as the extent to which such a medical expense might be covered by insurance. No doubt all questions will be answered in time, however.

Attaining FDA approval to begin the testing of embryonic stem cells required what has been described by many in the field as a herculean effort, which cost Geron more than $150 million dollars in preliminary research that was conducted over a span of 13 years. Now, many more years of expensive clinical trials will still be required before the FDA can consider approving Geron’s embryonic stem cells for availability on the U.S. market.

Geron Corp. was heavily involved in the funding of Dr. James Thomson’s laboratory at the University of Wisconsin at Madison in the 1990s, when Dr. Thomson became the first person to isolate an embryonic stem cell, first from a primate in 1995 and later from a human in 1998. Current plans at Geron are also in progress for the development of embryonic stem cells in the treatment of heart failure and in the growth of insulin-producing beta islet cells for the treatment of Type 1 diabetes.

Doctors in Germany have reported improvement in the cardiac function of a 2-year-old child who was critically ill with severe heart failure caused by dilated cardiomyopathy (DCM), and who improved after receiving autologous adult stem cell therapy.

Led by Dr. Stefan Rupp of the Pediatric Heart Center at Justus-Liebig University in Giessen, Germany, the team of physicians conducted an intercoronary administration of autologous adult progenitor cells derived from the infant’s own bone marrow. As described in their article, “DCM is the most common cardiomyopathy in childhood. Effectiveness of anticongestive therapy is limited in most cases and about one-third of children diagnosed with DCM die or receive heart transplantation within the first year after diagnosis.”

This case documents the first instance of an autologous adult stem cell treatment administered to a patient this young, whose condition was progressively worsening despite maximal anticongestive therapy prior to receiving the autologous adult stem cells, and who has consequently shown measurable improvement as a result of the autologous adult stem cells.

As the authors conclude, “Cardiac stem cell therapy proved to be technically feasible, was associated with improvement in cardiac function, and might represent an option before heart transplantation in children with severe heart failure.”

At the International Regenerative Biomedical Technology Conference in Dubai, a U.S. physician presents the clinical results of adult stem cell therapy that was successfully used in the treatment of a number of patients with cardiovascular disease.

Zannos Grekos, M.D., chief medical officer of the Florida-based stem cell center Regenocyte Therapeutic, presented data before the Dubai Congress on Regenerative Biomedical Technologies which demonstrated the successful treatment of several end-stage cardiac diseases in a number of patients via autologous (in which the donor and recipient are the same person) adult stem cell therapy. The evidence that he presented included PET scans, nuclear scans and echocardiographs performed at 6 months and one year post-treatment, all of which confirm the regeneration of damaged heart tissue including newly stimulated angiogenesis and improved heart function in patients who were treated with their own adult stem cells that were extracted from their own blood.

As Dr. Grekos stated, “This is real science, real medicine and real results. We have moved beyond bench research and clinical trials to show that the power of the body’s adult stem cells can be harnessed. Our success rate in reversing ischemic cardiomyopathy and congestive heart failure is extremely high and with our latest technology we’re capturing the same astounding cell regeneration results in other disease classifications.”

Additionally, Dr. Grekos announced that his team of physicians and scientists also used autologous adult stem cells in the successful treatment of a patient with Fabry disease, which is caused by an enzyme deficiency that leads to heart and kidney failure and which previously has had no cure. Whereas an ejection fraction (EF) of 55 is considered normal for healthy patients, this particular patient with Fabry disease experienced an EF improvement from 28 to 41 in just four months after receiving the autologous adult stem cell therapy. According to Dr. Grekos, “The patient no longer needs a heart transplant, which was previously the only means for arresting this disease. His kidney dialysis time has already been reduced by 10%, so we are looking at treating his kidney function in the near future.”

Dr. Athina Kyritsis, chair of Regenocyte’s medical advisory committee, states, “As a physician I find one of the most exciting things this discovery offers is the potential to address many diseases currently believed to be untreatable. We are leaping off of medicine’s cutting edge. This is no longer just theory.”

The procedure involves the simple drawing of blood from which the adult stem cells are isolated and then expanded in the laboratory and administered to the patient a week later either through an injection or infusion delivery system. Because the stem cells are autologous (meaning that the donor and the recipient are the same person), there is no risk of immune rejection.

In addition to being the chief medical officer for Regenocyte Therapeutic, Dr. Zannos Grekos is associate clinical professor of cardiology for Nova Southeastern University and has been appointed to the Science Advisory Board of the Washington, D.C. based Repair Stem Cell Institute. In 2007, Dr. Zannos was invited to brief the United States Senate Health Advisory Staff on the current state of stem cell research and therapy. Regenocyte Therapeutic is currently using adult stem cell therapy to treat congestive heart failure, cardiomyopathy, peripheral artery disease, coronary artery disease, kidney disease, ischemic heart disease, pulmonary disease and early senile dementia. Clinical trials will begin in 2009 for patients with macular degeneration and various neurological diagnoses.

Mesenchymal stem cells (MSCs) are clinically attractive for a number of reasons which include, among other desirable qualities, their ease of intravenous administration, their ability to home-in on injured tissue, their proven ability to differentiate into a wide variety of tissue types, and their status as immune privileged “universal donor” cells, for which they are especially well known. Numerous clinical trials throughout the U.S. are currently in progress in which MSCs are intravenously administered to patients with a vast range of conditions, thereby validating MSCs as an already well-established and viable therapy. Especially in the treatment of myocardial infarction, allogeneic (in which the donor and recipient are different people) MSCs as a clinical therapy have yielded statistically significant benefits in cardiac patients.

Nevertheless, despite the already high level of success enjoyed by MSCs, scientists have been trying to improve the therapeutic efficacy of these highly potent adult stem cells even further. Now, through a process of molecular potentiation, a team of researchers has succeeded in attaining the goal.

Using MSCs which were modified to overexpress IGF-1, Dr. Husnain Haider and his colleagues at the University of Cincinnati in Ohio observed an overall improvement in cardiac regeneration which was associated with increased mobilization of endogenous bone marrow stem cells in an animal model of heart attack. The MSCs were transfected with this insulin-like growth factor gene, which previously has been found to play an important role in the efficacy of MSCs in a variety of therapeutic uses, including the reversal of kidney failure. Now Dr. Haider’s study indicates that the IGF-1-transfected MSCs also possess superior efficacy in inhibiting pathological changes in rats following myocardial infarction, through the CXCR4 (a CXC chemokine receptor) signaling mechanism in the paracrine release of SDF-1-alpha (stromal-derived-factor being a chemotactically active molecule for lymphocytes), which promoted improved survival and engraftment by the MSCs in the infarcted cardiac tissue. Among other roles, CXCR4, also known as fusin, is specific for SDF-1 (also known as CXCL12) and has been identified in the homing ability of hematopoietic stem cells, and is already recognized as an important receptor in a wide variety of molecular processes.

Dr. Haider’s results corroborate a recent study conducted by Dr. Kondo of Japan, in which angiogenesis from exogenously administered bone marrow stem cells in an animal model of critical limb ischemia was found to be highly dependent upon the moblization of endogenous bone marrow stem cells which were activated by the exogenous stem cells. Now Dr. Haider’s group has observed that the ability of the exogenously administered MSCs to repair cardiac tissue and to inhibit further post-infarct pathological changes following a heart attack is also dependent upon the mobilization of endogenous bone marrow stem cells.

The role of IGF-1 in mobilizing endogenous bone marrow stem cells through paracrine activation of SDF-1-alpha/CXCR4 signaling, thereby increasing and improving the therapeutic efficacy of MSCs, is a discovery which may also prove to have additional applications in the potentiation of other types of stem cells.

Known as The Marvel Study, clinical trials are currently underway on two continents for the largest study ever to be conducted in the treatment of congestive heart failure with adult stem cells. Directed by Dr. Alan Niederman of the Jim Moran Heart and Vascular Research Institute at Holy Cross Hospital in Miami, the study consists of 330 patients who are enrolled in the trials at 30 separate investigational sites throughout the U.S. and Europe. The study involves the exclusive use of autologous adult stem cells as therapy.

The stem cells are drawn from each patient’s own thigh muscle and injected directly into the heart. According to Dr. Niederman, “This is what’s known as the pivotal study. If this study is positive, they will go to the FDA to approve this technique as a broad technique that everybody can particupate in.”

Previous studies indicate that improvement is often seen in the patient within a few weeks after receiving the stem cell therapy.

Aldagen, Inc., a biopharmaceutical company specializing in the development of proprietary regenerative cell therapies, reports the commencement of Phase III clinical trials for their newest and most advanced adult stem cell product. Known as ALD-101, and believed to be able to accelerate neutrophil and platelet engraftment following cord blood transplantation, the product was developed from adult stem cells that were isolated from umbilical cord blood. 40 pediatric patients with inherited metabolic diseases who have been selected for the study will receive a cord blood transplant in combination with ALD-101. In previous Phase I and II clinical trials, 24 patients who received ALD-101 showed a statistically significant reduction in platelet engraftment time when compared to controls who had not received ALD-101.

A number of inherited metabolic diseases have already been shown to be treatable with adult stem cells derived from cord blood, including Adrenoleukodystrophy, Metachromatic Leukodystrophy, Krabbe’s Syndrome and Hurler Syndrome, all of which have few treatment options and are often fatal. Now, products such as these developed by Aldagen offer yet a further improvement in the efficacy of such therapies.

In addition to ALD-101, Aldagen also has several other adult stem cell products which include ALD-151, which is designed to improve cord blood transplants in the treatment of leukemias, ALD-301 which was developed for the treatment of critical limb ischemia, and ALD-201 which was developed for the treatment of ischemic heart failure.

Mesenchymal stem cells (MSCs) are of great therapeutic interest because they are already known to be not only regenerative but also immune privileged and immune modulatory, unlike most stem cells. Such characteristics eliminate any need for matching MSCs immunologically to the recipient, and because of these "immune privileged" properties, the biotech company Osiris Therapeutics holds a number of patents on MSCs for a variety of allogeneic uses of MSCs such as the intravenous delivery of these stem cells in the treatment of patients with heart failure. Now the extraordinary properties of MSCs have been applied to yet another medical application, namely, to expediting the process of wound healing.

Dr. Yoshikawa and colleagues at the Nara Medical University in Japan have successfully mimicked an artificial dermis layer by culturing bone marrow-derived MSCs on a collagen sponge from which the layer of dermal cells was then implanted subcutaneously into an immune-compromised mouse and explanted after ten days, at which time histological examination revealed the differentiation of the MSCs into dermal tissue in vivo.

The procedure was then applied to 20 human patients who were suffering from pathological skin conditions that were refractory to conventional medical therapies, and for whom the same type of autologous "grafts" were applied to the wound areas after having been created from each patient’s own bone marrow-derived MSCs and the collagen matrix. From this procedure, 18 of the 20 patients were found to have significantly improved.

The procedure offers a promising new therapy for even some of the most severe types of wounds.

The administration of adult bone marrow stem cells (BMC) and mesenchymal stems cells (MSC) can aid in the recovery of myocardial infarction (MI) – commonly known as heart attack – and consequently increase survival rates according to a study in the Clinical and Experimental Pharmacology and Physiology published by Wiley-Blackwell.

The study is designed to evaluate the impact of systemic delivery of BMC and MSC on spontaneously hypertensive rats induced with MI.

Dr. Nardi, the lead author of the study called,

An unprecedented feat that could signal the beginning of the end of organ shortages has been achieved by doctors who have stripped down and refurbished a dead heart so that it can beat again.

According to the American team, the shortage of replacement hearts and other organs could be overcome with the new research. The need for anti-rejection drugs could also be completely avoided.

The research, conducted by researchers at the University of Minnesota, could pave the way to a new treatment for the 22 million people worldwide who live with heart failure. The journal Nature Medicine described the the world’s first beating, retooled “bioartificial heart”.

To begin, cells were removed from a whole heart. The blood vessel structure, valves, chambers, and full architecture of the heart were left intact, and repopulated with new cells.

“We just took nature’s own building blocks to build a new organ,” says Dr. Harald Ott, a co-investigator who now works at Massachusetts General Hospital. “When we saw the first contractions we were speechless.”

The work has huge implications: “The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells,” said Professor Doris Taylor, director of the Center for Cardiovascular Repair, Minnesota, principal investigator.

Virtually any organ with a blood supply could be created with the new method. The list includes the pancreas, lungs, kidneys, and liver.

Although costs make it prohibitive at present, Taylor is ready to grow a human heart. But she admits that the method is “years away” from being used in hospitals.

“We could begin with human cells and pig or human scaffold now but creating the larger bioreactors (the vessels in which the organs are grown) and generating the reagents and growing enough cells would cost tens of thousands of dollars for each heart at this point.”

“That is just too expensive to answer basic questions. We of course want to move in that direction, but funding is limited. As we can we will go forward – perhaps one heart at a time.”

Individuals face life long immunosuppression after an organ transplant. And over the long term, kidney failure, diabetes, and high blood pressure are the trade off for heart failure when using drugs to prevent rejection. Even getting to the point of performing the transplantation operation is difficult since donor organs are limited.

Researchers believe a new heart created by decellularization is much less likely to be rejected by the body since the heart is filled with the recipient’s own stem cells.

And once placed in the recipient, in theory the heart would be nourished, regulated, and regenerated similar to the heart that it replaced.

“We used immature heart cells in this version, as a proof of concept. We pretty much figured heart cells in a heart matrix had to work,” Professor Taylor says. “Going forward, our goal is to use a patient’s stem cells to build a new heart.”

As for the source of the cells from a heart patient, she says: “From muscle, bone marrow, or heart; depending on where the science leads us.”

Professor Taylor says that decellularization shows potential to change how scientists think about engineering any organ, even though heart repair was the initial goal.

“It opens a door to this notion that you can make any organ: kidney, liver, lung, pancreas – you name it and we hope we can make it,” she added.

According to UK Transplant, 81 people are waiting for heart transplant. Even though 28 patients died while waiting for a transplant last year, 155 patients had their lives saved or transformed by a heart transplant.

Typically, only 3,000 transplants are performed every year, despite more than 9,000 patients making up the waiting list nationally. While waiting, 1,000 people died last year.

A UK Transplant spokesman says: “These developments offer long term hope and long may they continue but the real problem now is a desperate shortage of donated hearts.”

Dr. Tim Chico, Consultant Cardiologist, University of Sheffield, says: “This is an ingenious step towards solving a massive problem. Heart failure (an inability of the heart to pump sufficient blood, usually after a heart attack) is increasing in the UK.”

“A chronic shortage of donors for heart transplantation makes stem cell therapy appealing. The study is very preliminary, but it does show that stem cells can regrow in the ‘skeleton’ of a donor heart. However, it will take a lot of further work to assess whether this will ever be a viable option for patients.”

Professor Wayne Morrison, Director of the Bernard O’Brien Institute of Microsurgery, Melbourne, comments: “This is the first time a whole organ has been tissue engineered outside the body.”

“They have demonstrated that they can create a heart that looks like a heart and is shaped like a heart and, most excitingly, that they can re-establish the blood vessels that were originally there. It is this ‘regrowth’ of the blood vessel cells that gives the potential in the future to connect this structure to a blood vessel in the body and then get circulation to go through it.”

“This very exciting study,” comments Dr. Jon Frampton, University of Birmingham. “Although this is only a first step requiring considerable follow-up development, the study nevertheless represents an exciting breakthrough that will eventually make the prospect of repairing damaged hearts a reality and will also be an approach that can be extended to other organs.”

Dr. Anita Thomas at the Australian Institute for Bioengineering and Nanotechnology, University of Queensland, adds: “There is one more major step to achieve before we can proceed any further: we need to see what happens when these artificial hearts are placed in a recipient animal for any length of time. The authors of the article have the necessary skills and yet have not reported their results. We wait with anticipation for their next publication.”

There have been advances in growing heart tissue in the laboratory but the complex architecture and intricacies of the body’s primary pump have to be mimicked exactly in order to be fully successful. Until now, the problem has been how to create a 3D scaffold that could do this.

This is why “decellulariazation” became the method of choice for Professor Doris Taylor and her colleagues. The process leaves only the extracellular matrix, the framework between the cells, intact, along with the plumbing and heart valves. This is accomplished by using a detergent to remove all the cells from the organ – in this case, an animal cadaver heart.

Taking immature cells that came from newborn rat hearts, researchers injected rat hearts with this mixture and placed the structure in a sterile chamber in the lab to grow. This was done after first removing the cells from both rat and pig hearts using a detergent.

Professor Taylor said the results were very promising. Contractions were observed in the hearts four days after seeding the decellularized heart scaffolds with cells. Even though it was only at two percent of the efficiency of an adult heart, the hearts were pumping eight days later.

A study at of the hearts at the cellular level revealed that the “cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue.”