April 17, 2009 by

NIH Issues Guidelines Restricting Embryonic Stem Cell Research

In response to President Obama’s March 9th Executive Order, the U.S. National Institutes of Health (NIH) have issued the first draft of a set of guidelines suggesting how federal funds should, and should not, be used for human embryonic stem cell research. The scientific, medical and religious communities have eagerly awaited the release of these guidelines, which have been highly anticipated, and debated, by all.

Specifically, the guidelines state that federal funds may now be used for research conducted on any human embryo that is “stored” at an IVF clinic and which is considered to be “spare”, “left-over”, or “orphaned”, after having been originally created at an IVF (in vitro fertilization) clinic for reproductive purposes. In other words, researchers may now apply for NIH grants to pay for such research – NIH grants being one of the primary, though certainly not the only, source of biomedical research funding throughout the United States. Nevertheless, contrary to public misconception, the NIH guidelines still prohibit the use of federal funds for research conducted on human embryonic stem cells derived from human embryos that were created by other means and for other objectives, such as, for example, somatic cell nuclear transfer, parthenogenesis, therapeutic cloning, and in vitro fertilization specifically designated for research or experimental, not reproductive, purposes.

It has been estimated that approximately 500,000 human embryos are currently frozen in a state of perpetual “limbo” in freezers at IVF clinics throughout the U.S., and many people, including the legal parents of these frozen “orphaned” embryos, are wondering what should be done about the situation. If any of the embryos were to be implanted into the uterus of an adult human female, many of the embryos would develop into a normal fetus and would ultimately be born as a human child, although some percentage of the embryos would either fail to implant properly or would fail to develop normally and would therefore not result in a healthy birth. When a woman solicits the services of an IVF clinic, usually for reasons pertaining to infertility, in order to be implanted with an embryo that was created through in vitro fertilization, it is standard procedure for the doctors of the IVF clinics to create multiple embryos with the IVF technique, precisely because of the fact that not every embryo will successfully implant and develop into a normal, healthy birth. The consequence of this routine, unquestioned practice is the creation of an unseen population of approximately half a million human embryos that nobody wants and which are destined either to be frozen indefinitely, discarded as biological trash, or now, as a result of the new NIH guidelines, deliberately destroyed in the process of embryonic stem cell research. The ethical can of worms that has been unleashed merely by the fact that these “orphan”, frozen human embryos exist, is beyond the scope of this news article to address, and possibly even beyond the scope of NIH to address. However, certainly one of the topics which NIH has yet to define precisely are the legal terms and conditions of the consent forms that parents of these frozen embryos must sign before their embryonic offspring can be officially designated for laboratory research and destruction.

Regardless of the specific legalities, embryonic stem cell scientists will now be allowed to receive federal funding (i.e., from NIH) for research which they may now perform on any of these “orphan” human embryos that are available from IVF clinics, all of which were originally created for reproductive purposes in the hopes of creating a human child, but which are “no longer needed for that purpose,” according to NIH acting director Dr. Raynard Kington. Although there are approximatley half a million orphaned human embryos frozen in IVF clinics across the U.S., it has been estimated that only approximately 700 new stem cell lines from those embryos would now be available for human embryonic stem cell research. Certainly 700 represents a significant increase from the number of human embryonic stem cell lines that were initially available in 2001 for federally funded research under the Bush administration, which originally had been estimated in the 60s but later proved to be numbered in the 20s. It is a common misperception, however, that President Obama has made broad, sweeping changes that will suddenly allow for any type of human embryonic stem cell research, as this is not the case, or at least not yet. The creation of human embryos specifically for research, not reproductive, purposes, is precisely what embryonic stem cell scientists covet the most, yet the federal funding of this type of research still remains illegal under the Obama administration, at least so far. Many proponents of adult stem cell research fear, however, that even this policy may, in time, change.

The new NIH guidelines allow for federal funding to be used for the very thing that is banned by the Dickey-Wicker Amendment, namely, research in which the health or life of a human embryo is threatened or destroyed. Although many people expect the Dickey-Wicker Amendment to be formally overturned at some time during the Obama administration, these NIH guidelines represent a concrete and immediate step in that direction. If Congress does, in fact, rescind the Dickey-Wicker Amendment, then the legalization of therapeutic cloning and other scientifically dangerous as well as ethically controversial procedures are seen as the logical next step. According to bioethicist Wesley Smith, “The political campaign has begun to destroy the Dickey Amendment. Should that happen, it would be legal for the Feds to fund human cloning, the making of embryos for research, and just about anything ‘the scientists’ wanted to do in this regard. Once that happens, the NIH would likely revise these guidelines to permit funding for those activities… Expect the struggle over Dickey to erupt within the next few years during the annual budgetary process. And if a bill passes sans the Amendment, there is no question in my mind that Obama would sign it.”

President Obama’s March 9th Executive Order directed NIH to submit guidelines addressing both the scientific and the ethical concerns of human embryonic stem cell research, within 120 days of that Executive Order, and NIH has issued this eagerly-awaited first draft in slightly over a month. According to NIH acting director Dr. Kington, “We considered the range of ethical issues and we believe this policy will allow the substantial research that is ethically responsible and scientifically worthy. We believe this is our best judgment now about a reasonable policy at this time.”

Apparently, a number of people disagree with Dr. Kington, such as, for example, Tony Perkins, president of the Family Research Council, who states, “The NIH draft guidelines demanded by the President will do nothing to advance stem cell research that is showing near-term benefit for suffering patients. Instead of funding more embryo destructive research, the government should fund research using adult stem cells that are on the cutting edge of treating patients for diabetes, spinal cord injury, heart disease and various cancers. Unfortunately, this draft guidance only diverts limited federal resources to unethical stem cell research that has not successfully treated a single person for any disease.”

Although embryonic stem cell proponents like to think that Obama’s policy on expanding embryonic stem cell research is a sign of “progress”, already Obama’s embryonic stem cell policy would appear to be outdated. It was nearly two years ago, on September 21st of 2007, that Dr. James Thomson was quoted in the Boston Globe as stating, “The world has changed. Over time, these [iPS] cells will be used in more and more labs. And human embryo stem cell research will be abandoned by more and more labs.” Dr. Thomson, of course, was the first person ever to isolate an embryonic stem cell in the laboratory, first in 1995 from a nonhuman primate and then in 1998 from a human. The entire field of embryonic stem cell research exists, therefore, purely as a result of Dr. Thomson’s achievements, and his name is revered in stem cell laboratories throughout the world. If anyone would understand the future direction of embryonic stem cell research, it would be Dr. Thomson. By sharp contrast to embryonic stem cells, the recently developed iPS (induced pluripotent stem) cells hold much greater research and clinical potential than do embryonic stem cells. Furthermore, since iPS cells can be created without involving an embryo at all, let alone destroying an embryo, iPS cells do not involve any of the ethical dilemmas that are inextricably entangled in embryonic stem cell research. Additionally, Dr. Ian Wilmut, who created the world’s first cloned mammal, Dolly the sheep, was quoted in Time magazine in December of 2007 as stating, “Changing cells from a patient directly into stem cells has got so much more potential”, once again referring to the advantages of iPS cells when compared to embryonic stem cells. Along those same lines, Dr. Shinya Yamanaka, who first developed iPS cells, was quoted in the December 11th, 2007 issue of the New York Times as stating, “We can’t keep destroying embryos for our research. There must be another way.” Apparently, neither President Obama nor the distinguished scientists at NIH have sought the advice of any of the world’s foremost leading authorities on embryonic stem cell research, cloning, nor iPS cells.

As stated on the website of the NIH, “The purpose of these draft Guidelines is to implement Executive Order 13505 on March 9, 2009, as it pertains to extramural NIH-funded research, to establish policy and procedures under which NIH will fund research in this area, and to help ensure that NIH-funded research in this area is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. Internal NIH procedures, consistent with Executive Order 13505 and these Guidelines, will govern the conduct of intramural NIH research involving human stem cells.” This first set of guidelines by NIH is only a draft, which will be published next week in the Federal Register where public comments from the general population will be accepted for the next 30 days. As also stated on the NIH website, “The National Institutes of Health (NIH) is requesting public comment on draft guidelines entitled ‘National Institutes of Health Guidelines for Human Stem Cell Research’ (Guidelines).” Apparently, members of NIH believe that it is possible for scientific and bioethical matters to be decided democratically, by majority opinion. Based upon the input of these public opinions, NIH is then expected to issue a final set of guidelines by early July.

(Please see the related news articles on this website, entitled, “Former Director of NIH Explains Why Embryonic Stem Cells are Obsolete”, dated March 4, 2009; “Obama Decrees Changes in Embryonic Stem Cell Research, Though Not What One Might Expect”, dated March 9, 2009; “Obama Rescinds Bush-Era Executive Order Pushing for More Ethical Stem Cell Research”, dated March 10, 2009; “Obama Signs Law Restricting Federal Funding of Embryonic Stem Cell Research”, dated March 11, 2009; “A High-Profile Proponent of Embryonic Stem Cell Research Sharply Criticizes Obama’s Policy”, dated March 13, 2009; and “Members of The President’s Council on Bioethics Object to Obama’s Stem Cell Policy”, dated March 26, 2009).

Filed Under: News, Spinal Cord Injury, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
April 16, 2009 by

Adult Stem Cells Treat Stroke Patients in Clinical Trial

After suffering a stroke on March 25th, 61-year-old Roland “Bud” Henrich arrived at the hospital too late to be given tPA (tissue plasminogen activator), the only previously existing treatment for ischemic stroke. He therefore became the first person to be enrolled in a clinical trial in which autologous adult stem cells are used for the treatment of stroke.

Nine more patients will be enrolled in the FDA-approved, NIH (National Institutes of Health) funded Phase I clinical trial, all of whom will be treated within 24 to 72 hours after showing initial stroke symptoms.

According to Dr. Sean Savitz, the lead investigator of the clinical trial and an assistant professor of neurology at the UT-Houston Medical School, “It’s still very early in this safety study, but this could be an exciting new therapeutic approach for people who have just suffered a stroke. Animal studies have shown that when you administer stem cells after stroke, the cells enhance the healing. We know that stem cells have some kind of guidance system and migrate to the area of injury. They’re not making new brain cells but they may be enhancing the repair processes and reducing inflammatory damage.”

In the study, autologous (in which the donor and recipient are the same person) mesenchymal stem cells are derived from each patient’s own bone marrow, and then readministered intravenously. Because the stem cells are autologous, there is no risk of immune rejection.

Approximately 800,000 people per year suffer a stroke in the U.S. alone, where stroke ranks as the third leading cause of death, after heart disease and cancer. Approximately one person every 40 seconds suffers a stroke, and approximately one person every 3 minutes dies from a stroke.

As Dr. Savitz explains, “This will be our first attempt to look at the safety of using stem cells in acute stroke patients. There’s a lot of promise behind this but we want to do it in a slow, rigorous fashion. Because we are injecting them intravenously, these cells can disperse to lots of different parts of the body and that’s why we’re looking at safety parameters.”

Already Mr. Heinrich is showing significant improvement. When he first arrived at the hospital, he was unable to speak and had partial paralysis on the right side of his body. After less than two weeks of hospitalization and rehabilitation following the stem cell therapy, not only was he able to walk and climb stairs without assistance, but he also began to speak his first words and phrases again.

According to Dr. James Grotta, chairman of the Department of Neurology at the UT-Houston Medical School, “This study is the critical first step in translating laboratory work with stem cells into benefit for patients. If effective, this treatment could be helpful to a huge segment of stroke patients to reduce their disability. We are fortunate here at UT-Houston and the Texas Medical Center to have the resources needed to carry out this work, and to have attracted someone of Dr. Savitz’s caliber to lead this study.”

The study is open to patients who show symptoms of an immediate stroke and who are either admitted to the Emergency Center at Memorial Hermann-Texas Medical Center or through the UT Stroke Team.

Since 2006, the UT-Houston Medical School has also been conducting a similar study in which autologous adult stem cells are used in the treatment of children with acute brain injuries, at Children’s Memorial Hermann Hospital.

One of the leading clinical and research organizations in the world, the University of Texas Health Science Center at Houston was established in 1972 by the UT System Board of Regents and the Texas State Legislature. The Center brings together the Dental Branch, the Graduate School of Biomedical Sciences, the Medical School, the School of Public Health, the School of Nursing, the School of Health Information Sciences, the UT Harris County Psychiatric Center, and the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. As of 2008, the UT Health Sciences Center at Houston had received 220 NIH grants, thereby ranking 60th out of 535 in the NIH funding of domestic institutes of higher education. The Institute of Molecular Medicine is directed by Ferid Murad, M.D., Ph.D., who also created the new departments of integrative biology, pharmacology and physiology at UT and who coshared the 1998 Nobel Prize in Physiology or Medicine for his work with nitroglycerine and signaling molecules in the cardiovascular system.

Filed Under: Heart Disease, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
April 15, 2009 by

Equine Stem Cell Technique to be Tested in People

Achilles tendinopathies can cause severe distress in humans, but in horses such conditions can be fatal. Now, after having treated over 1,500 race horses with an autologous adult stem cell therapy that has demonstrated both safety and efficacy in the horses, researchers will begin testing the procedure on humans.

The privately owned British biotech firm MedCell Bioscience announced today that it would begin clinical trials within 12 months, and plans are also being formulated to conduct a larger study at several participating European hospitals in 2011. As with the horses, the human adult stem cell therapy will consist of autologous (in which the donor and recipient are the same individual) adult stem cells, thereby eliminating any risk of immune rejection.

According to Dr. Nicola Maffulli, an orthopedic surgeon and specialist in sports medicine, “The move from clinical veterinary to human medicine is inspiring and unusual. We normally see the translation happening the other way around. I am very excited to be involved in the human studies and hope that the results will herald a new era in the treatment of musculoskeletal soft tissue injuries. At present the management of human tendinopathy is more an art than a science, but this approach could potentially reverse that situation.”

A number of adult canine and equine stem cell therapies have already been used with great success for conditions that include, among other ailments, compressive spinal cord damage, bone fractures, diabetes, laminitis (an inflammatory hoof condition that is common in horses), arthritis, joint and cartilage injuries as well as diseases of the heart and liver. The use of autologous adult stem cell therapy is becoming increasingly popular in veterinary clinics around the world, and the U.S. biotech company Vet-Stem is frequently in the news for the consistent success that it achieves in the commercialization of this procedure. Likewise, a number of similar companies in other countries are also reporting similar success, such as MedCell Biotech in the U.K., which was originally formed as a spin-off from research conducted by surgeons at the Royal Veterinary College of London.

Filed Under: Heart Disease, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
April 9, 2009 by

Embryonic Stem Cells Reveal Clues About Myelin

Scientists in the Departments of Anatomy and Neurology at the School of Medicine and Public Health at the University of Wisconsin at Madison have reported the successful formation of oligodendrocytes from human embryonic stem cells (hESCs), with a few surprising discoveries.

Within the human central nervous system (CNS), oligodendrocytes are the neuroglia that are responsible for forming myelin, which is the dielectric, electrically insulating fatty sheath that covers the axons of neurons throughout the entire body, and which is essential for the transmission of electrical signals along nerve fibers. While Schwann cells supply myelin to the axons of peripheral nerves, oligodendrocytes supply myelin exclusively to the axons of the CNS, and several demyelinating diseases such as, most notably, multiple sclerosis, are a result of the deterioration of the myelin that ordinarily is found within the CNS. Although degenerative conditions such as multiple sclerosis are known as “demyelinating” diseases, the problem is primarily with the oligodendrocytes, and secondarily with the myelin. Since myelin is approximately 80% lipid and 20% protein, nutrition is also known to play a crucial role in the maintenance of healthy myelin.

In the past, laboratory researchers have encountered a number of frustrating difficulties when trying to coax hESCs into oligodendrocytes, despite the fact that it has always been relatively easy to differentiate oligodendrocytes from mouse ESCs (mESCs). In mice, the production of oligodendrocytes is accomplished by exposure of the mESCs to a protein known as “sonic hedgehog homolog” (SHH), a ligand in the murine signaling pathway and a morphogen that has been well described in the regulation of vertebrate organogenesis and neurological organization. In hESCs, however, exposure to SHH was not enough to generate oligodendrocytes. As an aside, it is interesting to note that a number of scientists and clinicians alike continue to criticize the name of this homolog, which is an evolution of the original “hedgehog” gene that was first discovered in Drosophila melanogaster (the fruit fly) and which resulted in pointed projections that formed on the surface of Drosophila embryos whenever the gene was absent or inactivated, thereby resembling a hedgehog appearance in the embryos, which thus inspired the name. For discovering the hedgehog gene, Drs. Eric Wieschaus, Christiane Nusslein-Volhard and Edward B. Lewis were awarded the 1995 Nobel Prize in Physiology or Medicine. Currently 3 proteins have been identified in the mammalian “hedgehog” family, the other 2 besides SHH being “desert hedgehog” (DHH) and Indian hedgehog (IHH).

Now, Dr. Su-Chun Zhang and his colleagues at the University of Wisconsin at Madison may have discovered some of the reasons for the difficulties that scientists have typically encountered when trying to differentiate oligodendrocytes from hESCs. Among other things, the scientists found that exposure of the hESCs to SHH will, in fact, still result in the differentiation of the hESCs into oligodendrocytes, even though the differentiation process requires 14 weeks for hESCs as opposed to merely 2 weeks with mESCs. Paradoxically, however, one of the growth factors that promotes the differentiation of mESCs into oligodendrocytes, namesly, Fgf2 (fibroblast growth factor 2, also known as “basic fibroblast growth factor”, one of the 22 members of the structurally signaling molecules that comprise the FGF family), was surprisngly found to inhibit the differentiation in hESCs. Although Fgf2 has been known to play a key role in keeping hESCs in an undifferentiated state, the precise mechanisms by which this occurs have not yet been elucidated, nor is it understood exactly how Fgf2 promotes differentiation in mESCs.

As Dr. Zhang explains, “This was quite a surprise given that this is exactly how we direct mouse ESCs to become oligodendrocytes. But we have discovered an unexpected twist in the cell’s response to the same external factor. It nevertheless explains why so many research groups have failed to persuade human neural stem cells to become oligodendrocytes for the past decade.”

Dr. Zhang adds, “We are now able to generate a relatively enriched population of oligodendrocyte precursor cells that may be used to repair lost myelin sheaths. These findings also raise awareness of the direct translatability of animal studies to human biology. In this regard, the human oligodendrocytes generated from human ESCs of disease-induced pluripotent stem cells can provide a useful tool in the future for screening pharmaceuticals directly on human cells.”

Given the complexities inherent in the differentiation process from hESCs, and the uncertainties that still remain in controlling this process, it is therefore all the more impressive that other doctors and scientists, in studies unrelated to that of Dr. Zhang’s, have already achieved significant improvement in human multiple sclerosis patients using adult, not embryonic, stem cells. (Please see the related article on this website, entitled, “Adult Stem Cells From Fat Help Multiple Sclerosis Patients”, dated April 24, 2009, as reported in the Journal of Translational Medicine).

Indeed, with numerous patients throughout the world who need treatment now, today – not ten years from now, nor even one year from now, nor even one month from now – the need for a viable clinical stem cell therapy for diseases and injuries grows increasingly urgent. While discoveries such as Dr. Zhang’s are extremely interesting from a scientific point of view, they offer little that is immediately translatable to the clinic, from a therapeutic point of view. For medical therapies that are already being used in real clinics by real doctors on real human patients with real human diseases, today, at this very moment, adult stem cells are the only stem cells that already constitute any type of clinical therapy.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
April 3, 2009 by

Heart Stem Cells Regenerate Cardiac Tissue Throughout Lifetime

In an unusual application of radioactive carbon-14 dating, scientists have made some interesting discoveries regarding the natural activity of cardiac stem cells and the innate ability of the human heart to regenerate its own tissue throughout the entire human lifespan.

At the Karolinska Institute in Stockholm, Sweden, stem cell scientists have capitalized upon the unfortunate fact that a number of radioactive substances were released into the earth’s atmosphere as a result of the above-ground nuclear weapons testing that was conducted during the Cold War era of the 1950s and early 1960s, during which time there was a sharp spike in atmospheric levels of radioactive carbon-14, among other chemicals. Even though such levels subsequently declined after the above-ground testing of nuclear weapons was banned, C14 still continued to find its way into the cells of the human body and all other living creatures for many years thereafter, along with additional products of thermonuclear explosion such as radioactive strontium-90 which was found in the deciduous teeth of North American children during the 1950s and 1960s. Also known as radiocarbon, C14 is a radioactive isotope of carbon which occurs naturally in the upper layers of the troposphere and stratosphere when nitrogen atoms absorb thermal neutrons as cosmic rays enter the atmosphere. In the upper atmosphere, however, C14 does not present much harm to humans, whereas on terra firma it can be extremely harmful to any living organism, human or otherwise, when absorbed in sudden, high dosages by bodily tissue. With a half-life of approximately 5,730 years, C14 is not quickly “metabolized”, so to speak, and therefore has most typically been used as a reliable tool for calculating the age of organic archaeological remains, as it is readily absorbed by all living tissue. Indeed, as every first-year chemistry student knows, the presence of the element carbon is what distinguishes organic chemistry from inorganic chemistry, since biological life is not possible without carbon, and living creatures can just as easily absorb the radioactive carbon isotope into their bodily tissues as they can the regular carbon atom. Although C14 is one of the three naturally occurring carbon isotopes, it is the only one with an unstable nucleus as both C12 and C13 are stable isotopes.

Fortunately, the above-ground nuclear weapons testing that was conducted in several countries from 1955 to 1963 was finally halted as a result of the efforts of Dr. Linus Pauling who, along with his wife Ava, presented to the United Nations in 1958 a petition which called for an end to the above-ground testing and which was signed by more than 11,000 scientists from around the world. This petition, combined with subsequent pressure from the general public, resulted in an international moratorium on the testing and finally also the signing of the Test Ban Treaty in 1963 by U.S. President John F. Kennedy and Soviet Leader Nikita Krushchev. For his efforts in single-handedly mobilizing and leading such an effective public movement, Dr. Pauling received the 1962 Nobel Peace Prize, which was his second Nobel Prize, his first having been the 1954 Nobel Prize in chemistry for his elucidation of the chemical bond. Hence Dr. Pauling remains the only person ever to have won two unshared Nobel Prizes. After 1963, nuclear weapons testing continued but was transferred underground by the two major Super Powers of the Cold War era, so that radioactive fallout would not continue to contaminate the atmosphere and poison its inhabitants.

As with archaeological dating, C14 was used in this particular medical study as a cellular “clock” for measuring the age of cardiac cells in 12 deceased subjects whose ages at the time of death ranged from 19 to 73 years. Even in those individuals who had been born two decades prior to the start of nuclear weapons testing in the 1950s, C14 was still found to be abnormally elevated in their cardiac tissue, signifying that the tissue had absorbed the C14 years after birth. Similarly, in the younger deceased subjects, the C14 levels were also abnormally elevated but corresponded to a cellular age which was younger than the chronological age of the person, indicating a natural regeneration of the cells.

According to the results of this study, less than 50% of all cardiomyocytes are naturally regenerated by the heart throughout an entire human lifespan, and the rate of renewal slows with age. In the typical person who is 20 years old, for example, approximately 1% of all cardiomyocytes renew themselves each year, whereas in the typical 75-year-old person that percentage has decreased to around 0.45% of all cardiomyocytes. Mathematical modeling additionally revealed that those cells of the heart which develop into heart muscle have a lower turnover rate than do other types of heart cells, such as those that develop into blood vessels and connective tissue, which renew themselves at an annual rate of approximately 18%. Presumably it is the highly specialized nature of cardiac muscle which makes it so difficult to regenerate, since the unique electrical and mechanical properties of cardiac muscle distinguish it from all other types of muscle in the body. Precisely for such reasons, damaged heart muscle following heart attacks or traumatic injury has always been extremely difficult to heal and highly resistant to conventional therapeutic modalities.

Nevertheless, the natural potential for cellular regeneration in cardiac tissue is encouraging, albeit not statistically significant, and now scientists are turning their attention to the development of methods that might stimulate such a natural capacity.

As Dr. Jonas Frisen, a stem cell researcher at the Karolinska Institute in Stockholm who was involved in the study, explains, “We find that the beating cells in the heart, cardiomyocytes, are renewed. It has previously not been known whether we were limited to the cardiomyocytes we are born with or if they could be renewed. If we can understand how the generation of new cardiomyocytes is regulated, it may potentially be possible to develop pharmaceuticals that promote this process to stimulate regeneration after, for example, a heart attack.” Dr. Ratan Bhardwaj, also of the Karolinska Institute, adds, “A lot of people suffer from chronic heart failure, which is the result of heart cells dying. Maybe one could devise a pharmaceutical agent that would stimulate heart cells to make new and more cells to overcome the problem they are facing.”

The trick would be to increase the rate of regeneration to a level that exceeds the natural rate of cellular death, which is especially pronounced in some medical conditions which include chronic conditions such as heart failure and acute events such as a heart attack or traumatic injury. As Dr. Gregg C. Fonarow, professor of cardiology at UCLA, explains, “It was previously believed that the cardiomyocytes are terminally differentiated and cannot regenerate when the heart is damaged. Recent studies have suggested that cardiomyocytes can regenerate, but there has been substantial controversy as to the rate of cellular turnover. Whether there will be medical or gene therapies that can safely and effectively allow for higher rates of myocardial regeneration will require further study.”

According to Dr. Charles Murry, director of the Center for Cardiovascular Biology at the University of Washington in Seattle, “I am very excited about how they have used this novel technology to get something useful out of such a terrible environmental disaster.” Dr. Murry then adds, “A lot of us have been working on putting exogenous cells into the heart, but given the choice of growing my own heart back or taking all these cells from elsewhere, I would choose the pharmaceutical approach.” Not everyone shares such a personal preference, however, such as Dr. Joshua Hare, director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine, who cautions, “A drug may stimulate a biochemical pathway too crudely, and in regenerative medicine we need to be very careful to avoid unregulated cell growth that could cause tumors.”

Adult stem cells are known to reside throughout the human body and have been definitively discovered in a variety of tissue types, although the search for a cardiac stem cell had been an elusive one until recently. In 2008, however, researchers at Children’s Hospital in Boston identified a group of stem cells that differentiate into cardiomyocytes and which are located in the epicardium, which is the heart’s outer layer of tissue. Their findings were published in the June 22, 2008 issue of the journal Nature, corroborating similar discoveries in 2006 at both Children’s Hospital and Massachusetts General Hospital in Boston. Since then, independent researchers have also confirmed the presence of additional cardiac progenitor cells within the epicardium. (Please see the related article on this website, entitled, “Stem Cells Discovered in Surface of Heart”, dated June 22, 2008, as originally reported in the journal Nature).

Whether through pharmaceutical stimulation or through a more natural means, scientists hope to be able to harness the innate ability of the heart to regenerate its own tissue with its own endogenous stem cells, one way or another. The mere fact that the heart is capable of such a feat, which had previously been debated for so long, is no small discovery.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
April 1, 2009 by

Osiris Begins Phase II Clinical Trial With Adult Stem Cell Therapy for the Treatment of Heart Attack

Deep in the heart of Texas, the Heart Hospital of Austin is one of approximately 40 hospitals throughout the United States and Canada that have been chosen to participate in an FDA-approved clinical trial for the use of adult stem cells in the treatment of heart attack patients.

Specifically, the double-blind, placebo controlled Phase II clinical trial will evaluate the efficacy of an allogeneic adult stem cell product developed by the biotech company Osiris Therapeutics. Known as Prochymal, this proprietary adult stem cell therapy has already demonstrated exceptionally strong safety results in the Phase I clinical trial, during which time Prochymal was found to be even safer than a placebo. The current Phase II clinical trial will evaluate the ability of Prochymal to regenerate damaged heart tissue following a heart attack. The first patient to be enrolled in the clinical trial, a 58-year-old male, was already treated on Monday, within days of his heart attack. Approximately 20 patients will be enrolled in the study over the next 6 to 8 months, all of whom will receive the Prochymal treatment within 7 days of having suffered a heart attack. Prochymal is administered intravenously, and the entire therapy takes less than an hour to complete. Of the 40 hospitals that are participating in the clinical trial, only the Heart Hospital of Austin and one other hospital, in Kansas, have already begun treating patients.

According to 74-year-old Miles Simmons, who is also enrolled in the study in Austin and is scheduled to receive the Prochymal therapy, “I have a lot of grandchildren and I love them and I would like to spend more time with them. I think it’s wonderful. If you have technology, then use it.” As Dr. Roger Gammon, a cardiologist with the Heart Hospital of Austin and the director of the clinical trial, explains, “It would change everything for people with heart attacks. Research in this area has just exploded, and a lot of funding is going to have to come from the government to really push it forward. What’s kind of unique and new is it’s given intravenously. The cells are drawn to the heart and they implant there. If it works, it will be fantastic.”

Prochymal is composed strictly of adult stem cells, not embryonic stem cells. More specifically, Prochymal is composed of mesenchymal stem cells that are derived from the bone marrow of healthy adult donors. As such, not only is Prochymal entirely removed from the ethical controversies surrounding embryonic stem cells, but Prochymal is also free of the numerous medical risks posed by embryonic stem cells, not the least of which is the strong natural tendency of embryonic stem cells to form teratomas (tumors), which all pluripotent stem cells must, by definition, be able to form. By sharp contrast, since adult stem cells are not pluripotent, they are incapable of forming teratomas and do not pose such risks. Even though Prochymal is composed of non-autologous, allogeneic (in which the donor and the recipient are not the same person) adult stem cells, there is no risk of immune rejection since mesenchymal stem cells have been proven in multiple studies to be “immune privileged”, “universal donor” cells.

Nevertheless, embryonic stem cells remain a contentious issue, and on Friday of this week the Texas State Senate is scheduled to debate the topic of funding for embryonic stem cell research. According to Republican Senator Tommy Williams, “I think people agree that there’s the potential for moral hazard here, and so I think it’s important to give our state agencies and research institutions guidance.” The Texas state budget was passed on Wednesday, but no state funds will be used for embryonic stem cell research until the Legislature sets a policy.

Meanwhile, adult stem cell products such as Prochymal eliminate any need for debate. In a similar type of clinical trial, a hospital in Houston is also using adult stem cells for the repair of neurological tissue in stroke patients.

As Dr. Gammon adds, “We are excited to be the first to treat a patient in this groundbreaking study and to lead the way in this important research. Austin Heart and the Heart Hospital of Austin were selected because of their proven history of excellence in cardiovascular research and strong performance in the earlier Phase I trial. There’s a lot of enthusiasm in the cardiovascular community about the potential of stem cell therapies for treating heart disease. Earlier studies have established confidence in the safety of the therapy, but more research is needed to study its effectiveness.”

Osiris Therapeutics is the leading stem cell therapeutic company in the world, involved in the research and development of therapeutic products that are based exclusively upon adult stem cells, not embryonic stem cells. Osiris was founded in 1992 and went public in 2006. Its products focus on the treatment of inflammatory, orthopedic and cardiovascular conditions. The company’s proprietary adult stem cell product Prochymal is the only stem cell therapeutic product currently designated by the FDA as both an Orphan Drug and as a Fast Track product. In addition to the current Phase II clinical trial for the regeneration of cardiac tissue following myocardial infarction, Prochymal is also in Phase II clinical trials for the regeneration of pancreatic beta islet cells in patients with Type I diabetes and for the repair and regeneration of damaged lung tissue in patients with chronic obstructive pulmonary disease. Prochymal is also currently being evaluated in three separate Phase III clinical trials, two of which are for graft vs. host disease (GvHD) and the third of which is for Crohn’s disease, both of which are potentially fatal conditions. Additionallly, the company’s adult stem cell product Chondrogen has also been approved to begin Phase II and III clinical trials for osteoarthritis of the knee. Osiris currently has 47 U.S. patents, each with one or more foreign counterparts. In 2008 Osiris formed a strategic alliance with Genzyme worth approximately $1.3 billion, and that same year the U.S. Department of Defense awarded Osiris a contract to develop Prochymal as a treatment for acute radiation syndrome.

The Heart Hospital of Austin has been ranked the number one leading hospital in Texas for overall cardiac services for 6 years in a row, since 2004, during which time it has also ranked among the top 5% of hospitals in the nation for overall cardiac services, and in 2009 it was also chosen as number one among hospitals in Texas for cardiac surgery.

Filed Under: News, Osteoarthritis, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 30, 2009 by

Stem Cell Therapies Go to the Dogs, Horses and Camels

In his profession, job-related injuries are common. So when Buzz, a 3-year-old male Border Collie, was recently injured in his job, it looked as though his career was over. Responsible for the herding of sheep on a 40-acre working farm near Ramona, California, Buzz was faced with surgery and a recovery period of at least 6 months after rupturing a kneecap tendon. According to his owner, John Doyle, “His career was over. He was through.”

However, after undergoing the surgery to repair his tendon, Buzz then also received 3 rounds of autologous adult canine stem cell therapy. Instead of having to endure a 6-month recovery period, Buzz returned to work a mere 6 weeks after receiving the stem cell treatment. As Mr. Doyle explains, “In 2 weeks, you could see that he was healing very quickly. He was able to do a lot more.”

As previously reported a number of times on this website, the California-based company Vet-Stem is demonstrating consistent veterinary success in the treatment of animals with autologous adult stem cell therapy. Although Vet-Stem was the first company to commercialize the process, a number of other companies throughout the world are now also utilizing the same type of technology, in which adult stem cells are derived from each animal’s own adipose (fat) tissue and readministered to the animal as a clinical therapy for the particular medical condition from which the animal suffers. This type of autologous adult stem cell therapy has proven to be a highly preferable alternative treatment for many animals, especially those whose conditions require surgery or anti-inflammatory drugs, both of which can often be avoided with the stem cell therapy.

Vet-Stem was founded in 2002 as the result of stem cell research conducted at the University of Pittsburgh and UCLA in the late 1990s, when Dr. Bob Harman saw the commercial potential for veterinary applications of such stem cell technology. A veterinarian himself, as well as a statistician and former biotech entrepreneur who had already held the top executive title at 3 biotechnology companies prior to Vet-Stem, Dr. Harman is now the CEO of Vet-Stem as well as one of its founders. Based in San Diego, Vet-Stem patterned its initial clinical model upon the example of other companies that were already involved in human adult stem cell therapies, such as Cytori Therapeutics which had developed a proprietary separation apparatus that harvests human adult stem cells from adipose tissue at the patient’s bedside during reconstructive or cosmetic surgery. In a similar procedure, veterinarians extract approximately 2 tablespoons of adipose tissue from each animal, which are then sent to Vet-Stem where the adult stem cells are isolated, purified, expanded and returned within 48 hours to the veterinarian who then administers the stem cells to the animal.

Dogs are not the only animals to benefit from Vet-Stem’s veterinary technology, as horses and other larger animals have also been found to respond very well to adult stem cell therapies. In fact, among other partnerships, in September of 2007 Vet-Stem licensed their proprietary adult stem cell technology to the Central Veterinary Research Laboratory (CVRL) of Dubai in the United Arab Emirates, thereby allowing the CVRL to offer the same adipose-derived adult stem cell animal therapies throughout the Middle East. Sheik Mohammed bin Rashid al-Maktoum, the ruler of Dubai and the Prime Minister of the UAE, is an avid thoroughbred owner and a sponsor of the Dubai World Cup, the world’s most highly-prized horse race. As Dr. Harman described in 2007, “The Central Veterinary Research Laboratory will be an excellent partner in bringing this technology from the U.S. to the Middle East as they are already the most respected reference lab in the region.” CVRL now provides stem cell services for the treatment of injuries not only in thoroughbred race horses and Arabian endurance horses, but also in racing camels, among other species, throughout the Middle East. In the United States Vet-Stem has already treated over 3,000 horses and over 2,000 dogs with joint injuries and degenerative conditions that include tendon and ligament injuries as well as age-related osteoarthritis. Vet-Stem’s overall success rate is around 80% in the number of animals who are able to return to normal performance, a rate that is significantly above that of conventional surgical and pharmaceutical therapies.

Ordinarily, injuries of the bones, joints, tendons and ligaments result in scarring of the tissue, which not only prevents full healing but also often leads to further injuries at a later time. Conventional medical therapies do nothing to address the problem of scar tissue directly, and surgical procedures actually make the problem worse by increasing the severity of tissue scarring which in turn merely exacerbates later complications that will inevitably result from the scar tissue, since such tissue can never be fully rehabilitated. Stem cell therapy, however, allows for the full and complete healing of tissue without scarring, which not only reduces the risk of re-injury of the same tissue at a later date but also restores full physical performance and function, usually very quickly and dramatically. Such is the case in humans as well as in animals.

In fact, as Dr. Harman explains, “Our success in animals is directly translatable to humans, and we wish to share our evidence that stem cells are safe and effective.”

Vet-Stem uses exclusively adult stem cells, derived from each animal’s own tissue. Since the cells are autologous (in which the donor and recipient are the same animal), there is no risk of immune rejection. More specifically, the stem cells that are harvested in Vet-Stem’s procedure are mesenchymal stem cells, which are highly potent adult stem cells that are also found in bone marrow and umbilical cord blood. Numerous scientific and clinical studies have been published in the peer-reviewed medical literature detailing the regenerative properties of mesenchymal stem cells.

No embryonic stem cells are ever used in Vet-Stem’s therapies, since embryonic stem cells are highly problematic in the laboratory, whether they are of human or non-human origin. Among other problems, the risk of teratoma (tumor) formation disqualifies embryonic stem cells for use as a clinical therapy, even in animals. Adult stem cells, however, do not pose such risks and are therefore rapidly accumulating a consistent history of successful clinical treatments in veterinary, as well as in human, medicine.

Vet-Stem was initially funded by Toucan Capital of Maryland, which invests in early-stage life sciences companies and which provided an initial one million dollars in seed funding to Vet-Stem as well as an additional five million dollars to date. As with the other biotech companies that Dr. Harman has directed, Vet-Stem promises to be a highly profitable and sound investment, not only for its financial investors but also for its four-legged patients.

Filed Under: News, Osteoarthritis, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 28, 2009 by

Spinal Cord Injuries Treated With Adult Stem Cells

Researchers have published the results of a study demonstrating both the safety and the feasibility of an adult stem cell therapy for the treatment of both acute and chronic spinal cord injuries.

Scientists at the California-based company, DaVinci Biosciences, in collaboration with the Luis Vernaza Hospital in Ecuador, have conducted a clinical study in which 8 patients were treated with autologous (in which the donor and recipient are the same person) adult stem cells derived from each patient’s own bone marrow. The stem cells were then administered via a proprietary “multiple route delivery technique” to the 8 patients, 4 of whom suffered from acute spinal cord injuries and 4 of whom suffered from chronic spinal cord injuries. The routes of administration included delivery directly into the spinal cord, directly into the spinal canal and intravenously. Throughout the 2-year follow-up period, all 8 patients were observed to improve through the measurement of such parameters as regained mobility and sensation, regained bladder control and confirmation by sequential MRIs of actual morphological regeneration within the spinal cord itself. No adverse side effects were observed.

Approximately 400,000 people in the U.S. alone are estimated to suffer from spinal cord injuries, with approximately 11,000 new cases diagnosed each year. On average, 52% of all spinal cord injuries result in paraplegia while around 47% result in quadriplegia. According to Dr. Rafael Gonzalez, director of R&D for DaVinci Biosciences, “We are pleased to see the publication of our research. It represents a giant step in the process of improving the quality of life in people living with spinal cord injury and other neurodegenerative disorders.”

According to Francisco Silva, president of DaVinci Biosciences, “The outcome of this study is exciting for us and our patients. We plan on expanding and building upon the results. We strongly believe that this is an important first step for realizing the therapeutic application of stem cells for treating diseases and injuries such as spinal cord injury in humans.”

As Dr. Paul Sanberg, director of the Center of Excellence for Aging and Brain Repair at the University of South Florida, adds, “Although there have been numerous studies in animals demonstrating the benefits of stem cell treatment for spinal cord injury, this is the first published study of its kind. It gives patients the possibility that their quality of life can be improved.”

Headquartered in Costa Mesa, California, DaVinci Biosciences has additional facilities throughout North and South America and is involved in a number of parnerships with universities, medical research institutions and hospitals. DaVinci’s primary area of development is focused on cell-based therapeutics and small molecule compounds in the treatment of neurodegenerative disorders such as spinal cord injury, multiple sclerosis, Parkinson’s disease, and ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease). In collaboration with one of its partners, the company has patented a surgical technique for the effective delivery of cell-based therapies directly into the spinal cord. DaVinci Biosciences is divided into 2 main business units which include DV Biologics, the main research division, and DV Therapeutics, the development division which advances the molecular and cell-based technologies to therapeutic applications.

In the exploding field of regenerative medicine, this new study provides strong evidence that autologous adult stem cells derived from bone marrow offer a safe and feasible therapy which improves the quality of life for patients suffering from acute and chronic spinal cord injury.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
March 27, 2009 by

Act of Congress Offers Financial Incentive for Cord Blood Banking

Known as the “Family Cord Blood Banking Act”, new federal legislation in the United States will amend the I.R.S. (Internal Revenue Service) Code to allow couples and individuals to use “tax advantaged dollars” in order to pay for the banking of umbilical cord blood and the adult stem cells contained therein. Tax advantaged financial accounts such as FSAs (flexible spending accounts), HRAs (health reimbursement arrangements) and HSAs (health savings accounts), and variations thereof, will now be applicable to cord blood banking expenses.

The legislation was introduced yesterday in the U.S. House of Representatives by Ron Kind (D-WI), Artur Davis, (D-AL), Wally Herger (R-CA), Mike Thompson (D-CA) and Bill Pascrell Jr. (D-NJ). According to Representative Ron Kind, the chief sponsor of the legislation and a member of the House Ways and Means Subcommittee on Health, “This legislation supports families that choose this potentially life-saving investment by providing tax incentives for these medical expenses.”

A number of private companies have announced that they support the legislation, including the Cord Blood Registry (CBR), which offers collection and preservation services of adult stem cells derived from umbilical cord blood. Currently, families are arbitrarily restricted by tax laws in the use of tax advantaged dollars and in the tax deduction of medical expenses. According to David Zitlow, senior vice president of public affairs and communications at CBR, “Families may pay for over-the-counter cough syrups or heartburn pills using these dollars, but not cord blood banking services. These limitations are unfair and even unwise. Families who opt to deposit into tax advantaged health accounts should have the discretion to spend those dollars as they see fit on qualified medical expenses.”

According to Dr. David Harris, the scientific director at CBR and a stem cell researcher at the University of Arizona, “Research and clinical trials involving cord blood will require more children to have a source of their own cord blood stem cells available for transplant. Consequently, legislation that makes it easier for families to bank cord blood will definitely speed up the time-table for life-saving research and will allow scientists to unlock the vast potential of these amazing cells on a much quicker basis.”

According to Matthew Schissler, CEO and founder of Cord Blood America, an international umbilical cord blood stem cell preservation company, “This would allow individuals and couples to pay for umbilical cord blood banking services through health savings accounts, flexible spending accounts, medical expense tax deduction and health reimbursement arrangements.”

Numerous organizations are involved in raising the awareness of, and lowering the financial barriers to, adult stem cell therapies derived from cord blood. In addition to CBR, other groups who have announced their support of the Family Cord Blood Banking Act include the Coalition for Regenerative Stem Cell Medicine and their member associations which include the Brain Injury Association of America (BIAA), the Association of Nurse Practitioners in Women’s Health, the Parent’s Guide to Cord Blood Foundation, and the National Spinal Cord Injury Association (NSCIA), among others, as well as a growing list of other foundations, companies, university institutions, researchers and disease advocacy groups.

Umbilical cord blood has a history of clinical therapeutic use that predates World War II, and adult stem cells derived from umbilical cord blood have been used in over 14,000 transplants in the treatment of more than 70 different diseases just in the past 20 years alone. While donating to a public cord blood bank is free, private cord blood banking carries associated expenses which may be as high as $2,000 for the first year and $125 for each year thereafter. The advantage, of course, is that the donating family retains the right of exclusive access to their stem cells that are stored in private banks, whereas those who donate to public banks relinquish the right to any future access to their own stem cells. Now, however, the new legislation will lower the cost to families through the new tax incentives, which not only will allow more people to benefit from private cord blood banking but it should also increase the overall supplies of cord blood stem cells.

The harvesting of adult stem cells from umbilical cord blood is a safe and non-invasive procedure which begins with the simple collection of umbilical cord blood at the time of birth. The adult stem cells may then be used throughout the future not only as a therapy for the person who donated the cord blood, but also as a therapy for biological relatives of that person, and for anyone for whom such stem cells may be immunologically compatible.

The Cord Blood Registry (CBR) is the world’s largest stem cell bank. The company is involved exclusively in the collection, processing and storage of adult stem cells derived from umbilical cord blood for future medical use. CBR was the first family cord blood bank to be accredited by the AABB (the American Association of Blood Banks). CBR has been cash-flow positive since 1999 and has thus far stored and processed the umbilical cord blood of more than 260,000 newborns from around the world.

Filed Under: News, Spinal Cord Injury, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
March 25, 2009 by

First Clinical Trial With Human Stem Cells Approved In India

The stem cell company Stempeutics Research has received approval from the Drug Controller General of India (DCGI) to begin the first clinical trial ever to be conducted in India with human stem cells. Specifically, the clinical trial will use mesenchymal stem cells derived from bone marrow in the treatment of two separate conditions, acute myocardial infarction and critical limb ischemia.

According to Nagendra Swamy, the Chief Operating Officer of Manipal Hospital in Bangalore, “It will be a multi-centric placebo-controlled, double blind and allogeneic clinical trial. The aim is to address two diseases: acute myocardial infarction and critical limb ischemia. Since [adult stem cells] derived from a single donor can be manufactured to treat 10,000 patients, we expect the product will provide affordable treatment for all.”

The global market for stem cell therapy is projected to reach $20 billion by the year 2010, and currently the stem cell therapy market in India alone is estimated at $540 million.

In addition to myocardial infarction and critical limb ischemia, which is an advanced form of peripheral artery disease, Stempeutics is also currently developing adult stem cell therapies for the treatment of Parkinson’s disease, spinal cord injury, motor neuron disease, end-stage liver disease, various skin disorders and avascular necrosis.

Filed Under: News, Spinal Cord Injury, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
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