Researchers Report First Successful Creation of Heart Tissue From Adult Heart Stem Cells

Stem cells are known to reside in most types of tissue throughout the adult human body, but until recently it was believed that the heart is one region of the body which does not contain its own stem cells. Such a theory has now been proven to have been erroneous.

A number of recent studies have led to the identification of a small pool of stem cells that reside in the adult human heart, and now researchers in the Netherlands have successfully isolated these stem cells. Upon being cultured, the cells spontaneously developed into mature heart muscle that exhibits rhythmic contraction and is also responsive to electrical stimulation and adrenaline. According to Dr. Pieter Doevendans of the University Medical Centre in Utrecht, “We’ve got complete control of this process, and that’s unique. We’re able to make heart muscle cells in unprecedented quantities, and on top of it they’re all the same. This is good news in terms of treatment, as well as for scientific research and testing of potentially new drugs.”

Cardiac muscle is among the most specialized types of tissue in the body and is typically highly resistant to repair following damage such as that caused by a heart attack or acute injury. For this reason, conventional wisdom held that the heart must be devoid of stem cells, but now that it is known that the heart does in fact contain its own stem cells, further studies will investigate the precise role that such stem cells play in cardiac health and function. With the assistance of modern medical technology, such endogenous cardiac stem cells can ultimately be utilized in the treatment of heart disease and other cardiac problems.

Stem Cells From Menstrual Blood Offer New Hope in Organ Transplantation and in the Treatment of Numerous Diseases

Stromal cells are found in the endometrial lining of the uterus and are shed every month during menstruation. Stromal cells are also found in connective tissues throughout the body, and are known to differentiate into new cartilage, bone, fat, heart, skin and brain cells. Such cells are now the focus of intense research throughout the world, as the discovery of their presence in menstrual blood offers a new opportunity for easily and noninvasively collecting such prized cells. Known as MenSCs (menstrual blood stromal cells), these cells may be harvested from a potentially unlimited, inexpensive, and continuous source by methods that are free of ethical controversies.

According to Dr. Amit Patel, director of Cardiac Cell Therapy at the University of Pittsburgh’s McGowan Institute of Regenerative Medicine, “Uterine stromal cells have similar multipotent markers found in bone marrow stem cells and originate in part from bone marrow.” When the MenSCs were grown in the laboratory, the cells were found to divide very rapidly, even more rapidly than stromal cells that are harvested directly from bone marrow. Although MenSCs do not divide as fast as embryonic stem cells do, MenSCs also do not carry any of the risks that are associated with embryonic stem cells, such as the formation of a particular type of cancerous tumor known as a teratoma.

Cryo-Cell International was a partner in conducting the research. According to Julie Allickson, vice president of laboratory operations, research and development at Cryo-Cell, “The preliminary results are extremely encouraging and support the importance of further study of these cells in several different areas including heart disease, diabetes and neurodegenerative disease.” According to Dr. Dwaine Emerich, a section editor for Cell Transplantation, “These studies are a significant step forward in the development of transplantable stem cells for human diseases because they address major issues including routine and safe cell harvesting of renewable cells that maintain their differentiation capacity and can be scaled for widespread clinical use.”

It is believed that these rapidly dividing MenSCs may be of particular usefulness in those diseases that require organ transplantation. Instead of transplanting an organ that has been donated by someone, scientists will instead be able to grow a new organ, and the other new tissue that is needed, from MenSCs such as these.

These findings with MenSCs offer further substantiating evidence for the potency of endometrial regenerative cells (ERCs), the properties of which were first described by scientists of Medistem Laboratories, who published the first full elucidation of ERCs in the Journal of Translational Medicine in November of 2007 in an article entitled, “Endometrial Regnerative Cells: A Novel Stem Cell Population”. The Medistem scientists were then honored with an award by Biomed Central for the best research article of 2007 in medicine, which was presented at the Royal Society of Medicine in London in March of 2008.

Adult Stem Cell Company Selected for Prestigious Conference in Israel

Pluristem Therapeutics Inc., a biotech company specializing in the commercialization of allogeneic adult stem cell therapy for degenerative, ischemic and autoimmune diseases, has been selected to present at the First Annual Israeli Presidential Conference entitled, “Facing Tomorrow”, to be held from May 13 -15 in Jerusalem. A total of 60 presenters were selected from among hundreds of candidates in the sciences, the arts, and business, all of whom represent inventions and innovative ideas that have been developed by Israeli individuals and which have the potential “to revolutionize the future”, in the words of Conference representatives. According to Pluristem’s President and CEO, Dr. Zami Aberman, “Pluristem is pleased to be invited to this high level international conference to present its business and products in development to world-renowned business leaders, technology thought leaders and entrepreneurs.”

A number of world leaders in the arts, the sciences, business and politics will attend the Conference, including U.S. President George W. Bush, Former British Prime Minister Tony Blair, Former President of the USSR Mikhail Gorbachev, Former U.S. Secretary of State Dr. Henry Kissinger, New York Times columnist Thomas L. Friedman, Chairman and CEO of News Corporation Rupert Murdoch, and Harvard Law Professor Dr. Alan Dershowitz.

Pluristem Therapeutics is currently developing a variety of novel adult stem cell products in their pipeline which are derived from the human placenta. As such, the products are strictly non-embryonic and non-controversial. The products consist of expanded placental mesenchymal stromal cells (MSCs) which are immune-privileged and which exhibit immunomodulatory properties. For the expansion of these MSCs, Pluristem uses a proprietary 3-dimensional bioreactor which is modeled after the natural microstructure of bone marrow matrix. Their main product in development, PLX-PAD, is targeted toward those millions of people who suffer from peripheral artery disease (PAD). Other products include PLX-1, which improves the engraftment of hematopoietic stem cells derived from umbilical cord blood, and PLX-Stroke which is for the treatment of ischemic stroke, and PLX-MS which is for the treatment of multiple sclerosis.

Neural Stem Cells Discovered in Adult Human Spinal Cord

At the French National Institute for Health and Medical Research (INSERM), scientists have discovered the presence of neural stem cells in the human spinal cord. Although neural stem cells had previously been discovered in the brain and spinal cord of adult rodents several years ago, this marks the first discovery of neural stem cells in human brains and spinal cords. Such a discovery corroborates new supporting evidence that the human central nervous system (CNS) is in fact capable of regeneration – a radical idea which shatters the previously revered, though incorrect, dogma that the CNS is incapable of regeneration.

Using electron microscopy to detect neural precursor cell markers, the researchers at INSERM were able to identify and isolate adult neural stem cells from the human spinal cord. The stem cells were then cultured in vitro and found to differentiate into both neurons and glial cells. Research is now focused on the use of such endogenous neural stem cells in the treatment of neurodegenerative and demyelinating diseases such as multiple sclerosis and ALS (amyotrophic lateral sclerosis, or “Lou Gehrig’s disease”), as well as in the treatment of spinal cord injury (SCI). It is currently estimated that approximately a third of a million people throughout Europe, and a quarter of a million people in the U.S., suffer from SCI, with approximately 10,000 new cases occurring each year in each of these demographic regions. The majority of people who suffer SCIs are betweeen the ages of 25 and 30, and the resulting paralysis has often been regarded as permanent and irreversible.

Now, however, new hope is available as a reult of this important discovery that neural stem cells naturally reside within the CNS. According to Dr. Alain Privat, Research Director at INSERM, “This work constitutes a major step forward for all the pathologies affecting the motoneurons for which no treatment exists at the present time.”

The research was funded by the RESCUE (Research Endeavor for Spinal Cord in United Europe) Project, which in turn is funded by the European Commission FP6 Research Progrramme. RESCUE is a consortium of stem cell biologists and experts in spinal cord pathology from 9 European research centers, the mission of which is to advance novel stem cell therapies for spinal cord injury toward clinical trials. Known technically as translational medicine, such a process involves “translating” the results of experimental laboratory studies into clinical therapeutic paradigms. RESCUE researchers are dedicated to the implementation of such translational medical procedures specifically as applied to new therapeutic protocols for the treatment of SCI.

President Bush Addresses National Catholic Prayer Breakfast

Today in Washington, D.C., the fifth annual National Catholic Prayer Breakfast was attended by some preeminent politicians which included not only U.S. President George W. Bush but also GOP presidential candidate Senator John McCain of Arizona, as well as Senator Sam Brownback of Kansas and the U.S. Supreme Court Chief Justice John Roberts. While President Bush is a Methodist and Senator McCain is Episcopalian, both Senator Brownback and Chief Justice Roberts are Roman Catholic.

President Bush addressed the gathering on a number of topics, including his support of adult stem cell research over embryonic stem cell research. He acknowledged the importance of many recent scientific breakthroughs, including the reprogramming of adult skin cells so that they behave with the same pluripotency as embryonic stem cells. President Bush added, “We have stood fast in our belief that promising medical advances can co-exist with ethical medical practices.”

President Bush is often criticized for his ban on the federal funding of human embryonic stem cell (hESC) research, when, in fact, this point is often misunderstood. On August 9th, 2001, President Bush announced, via Presidential Executive Order in a televised address to the nation, that he was placing a ban on the federal funding of research conducted on any hESC lines established after that date; however, he also simultaneously approved the federal funding of research conducted on hESC lines that had already been established on or before that date. Prior to his administration, however, Congress had passed, and President Clinton had signed, legislation prohibiting the use of federal money for the destruction of human embryos for research purposes. By the time President Bush inherited the dilemma, he actually loosened the restrictions that were already in place under the Clinton administration, as President Bush responded by expanding the use of federal funds for research on those hESC lines that were already in existence. Nevertheless, further criticism resulted when, by 2005, it was estimated that only 16 of the original 78 hESC lines were viable for research, the others having been rendered useless through contamination and other problems. The NIH (National Institutes of Health) Stem Cell Registry was then created to document these existing hESC lines and their characteristics, as well as to test and assess the quality of these hESC lines.

Contrary to popular belief, this Presidential Executive Order, which only banned the use of federal funds for research conducted on hESC lines created after August 9th, 2001, does not prohibit research on hESC lines created after that date, as long as the research is sponsored by non-federal funds. Indeed, private funding thrives, and hESC research has continued and is currently taking place in numerous laboratories throughout the U.S., both in university and corporate biotech settings, but such research is funded by non-governmental sources. Many prominent scientists have created their own hESC lines after President Bush’s Executive Order, such as the Harvard biologist Dr. Doug Melton, who, in March of 2004, created 17 new hESC lines from private donations. Today he is co-director of the Harvard Stem Cell Institute, founded in 2004, where extensive hESC research is conducted entirely under the auspices of private sources. Similarly, many other places throughout the U.S., such as the Institute for Stem Cell Biology and Regenerative Medicine at the Stanford University School of Medicine, also conduct hESC research that is privately funded. The Presidential Executive Order that was issued on August 9th, 2001, did not stop hESC research in the U.S., nor was it intended to do so; instead, it merely excluded such research from being funded by taxpayers’ money.

Despite the fact that hESC research continues throughout the U.S., countless ethical questions surrounding embryonic stem cells remain unresolved, and the topic continues to be the focus of heated debate. A number of other countries besides the U.S. also impose restrictions on hESC research, and some of the organizations that are formally examining the ethical dilemmas of hESC research include:

The President’s Council on Bioethics,

The Kennedy Institute of Ethics at Georgetown University in Washington, D.C.,

The American Association for the Advancement of Science and the Institute for Civil Society, which together jointly issued the publication, “Stem Cell Research and Applications: Monitoring the Frontiers of Biomedical Research”,

The International Society for Stem Cell Research, which issued the publication, “The Ethics of Human Embryonic Stem Cell Research”, and

The EU Commission of the European Communities, which issued the publication entitled, “Report on Human Embryonic Stem Cell Research”.

Ethical issues aside, however, embryonic stem cells have proven to be extremely problematic in the laboratory, with numerous inherent risks and dangers not the least of which is the ability of embryonic stem cells to form a specific type of cancerous tumor known as a teratoma. Precisely for this reason, embryonic stem cells have never advanced beyond the laboratory stage, and have never actually been used to treat a single human disease or injury. By sharp contrast, however, adult stem cells are already being used in clinics around the world and have already been proven to be a viable therapy for the treatment of real human beings with real human diseases and injuries.

While it is most often within such venues as the National Catholic Prayer Breakfast that adult stem cell success stories are most enthusiastically welcomed and received, such news nevertheless deserves to be heard by everyone everywhere.

Stem Cells from Menstrual Blood Differentiate into Cells Resembling Cardiac Precursor Cells

Scientists in Japan have reported the discovery of cells that behave like cardiac precursor cells and which are derived from human menstrual blood. The discovery corroborates similar reports made independently by researchers in the United States in November of 2007. In both cases, such a discovery identifies a new, non-invasive, inexpensive, universally available, easily obtainable and ethically non-controversial source of highly potent stem cells.

As described by the Japanese researchers, these MMCs (menstrual blood-derived mesenchymal cells) “began beating spontaneously after induction, exhibiting cardiomyocyte-specific potentials.” The researchers hypothesized that the majority of the cardiomyogenic cells found in the MMCs had originated from detached uterine endometrial glands, 76 to 97% of which were shown to transdifferentiate into cardiac cells in vitro. Additionally, the MMCs were found to proliferate an average of 28 generations, while the subpopulation of EMCs (endometrial gland-derived mesenchymal cells) were able to be engrafted onto a recipient’s heart via a 3-dimensional EMC cell sheet. When the MMCs were transplanted into rats who had suffered myocardial infarction, cardiac function was significantly restored.

The authors concluded that, “MMCs appear to be a potential novel, easily accessible source of material for cardiac stem cell-based therapy.”

The findings were reported by scientists at the Keijo University School of Medicine in Tokyo in collaboration with researchers at the National Research Institute for Child Health and Development in Tokyo, the National Cancer Center Research Institute in Tokyo, Kanazawa University School of Medicine, and Tokyo Women’s Medical University.

Phase III Clinical Trials Begin With Cord Blood Stem Cells in the Treatment of Metabolic Disorders in Pediatric Patients

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.

Parathyroid Hormone Mobilizes Endogenous Stem Cells in the Treatment of Critical Limb Ischemia

An advanced form of peripheral artery disease (PAD), critical limb ischemia is often associated with high levels of morbidity and mortality. Patients who suffer from this condition often experience acute pain in the affected limbs, even while at rest. In the past, amputation has often been the unfortunate result of this disease.

Now scientists in Italy have been able to utilize the body’s own supply of endogenous stem cells in the treatment of critical limb ischemia in a mouse model. Employing the standard paradigm of femoral artery ligation in the mice, the researchers stimulated the mobilization of endogenous stem cells with G-CSF (granulocyte colony stimulating factor) both exclusively and in combination with parathyroid hormone.

Improvement was seen in the mice, most dramatically with the G-CSF and parathyroid hormone combination which was found to induce angiogenesis in the ischemic muscles.

Although clinical trials have already been conducted in human patients in the U.S. in which mesenchymal stem cells have been used to treat peripheral artery disease, these results with G-CSF and parathyroid hormone indicate that additional combinations of pharmaceuticals may further optimize patient improvement.

Adult Stem Cells Show Positive Results in a Pre-Clinical Study of Multiple Sclerosis

Pluristem Therapeutics Inc., which specializes in the commercialization of therapeutic products developed exclusively from adult mesenchymal stromal cells (MSCs) that are derived from the human placenta, has announced positive results with the use of one of its products in a pre-clinical animal study of multiple sclerosis. PLX-MS, which Pluristem is developing specifically for the treatment of multiple sclerosis, was tested in the EAE (experimental autoimmune encephalitis) animal model, which typically serves as the standard research paradigm for multiple sclerosis in humans. After EAE was induced in the animals, some of the animals were given PLX-MS while others served as controls. The animals that had received PLX-MS were found to show a statistically significant improvement in their EAE scores, which lasted throughout the entire 25-day duration of the study, when compared to the controls.

According to Dr. Zami Aberman, President and CEO of Pluristem, “We are very excited that our PLX cells were able to demonstrate beneficial results that are statistically significant in this standardized model for multiple sclerosis. These results, in addition to our previously announced PLX-Stroke results, demonstrate that PLX cells may be useful in the treatment of central nervous system disorders and may potentially help millions of people. Additionally, we believe this experiment demonstrates that we can potentially utilize our off-the-shelf, easy-to-obtain PLX cells and achieve results that are as good as or better than MSCs obtained from other more difficult-to-find sources.”

Multiple sclerosis, one of the demyelinating diseases, is a disorder of the central nervous system and is generally considered to be of autoimmune origin. According to recent estimates from the World Health Organization, over 2.5 million people around the world currently suffer from multiple sclerosis. Prior to adult stem cell research such as these studies conducted by Pluristem, multiple sclerosis has previously been considered incurable and irreversible. Now, however, adult stem cells and regenerative medicine offer a new type of therapeutic modality and, therefore, also new hope.

Cautionary Response Issued for Clinical Trials With Embryonic Stem Cells

Three biotech companies are currently preparing for their upcoming clinical trials that will test the therapeutic value of their proprietary embryonic stem cell products. In the midst of such preparation, the U.S. FDA (Food and Drug Administration) convened a panel of experts yesterday to examine the safety concerns associated with such proposed therapies, not the least of which is the risk of cancer.

It is a well-established fact that embryonic stem cells cause the formation of a specific type of cancerous tumor known as a teratoma; indeed, such a feature of embryonic stem cells constitutes their defining trait. An embryonic stem cell is a cell which, by definition, forms a teratoma, and this remains the universal laboratory test by which embryonic stem cells are identified throughout the world. This test is the global scientific standard of measurement: if a cell forms a teratoma, then it is recognized as being an embryonic stem cell; if a cell does not form a teratoma, then it is recognized as being just an ordinary adult stem cell or some other type of cell. Adult stem cells, by stark contrast to embryonic stem cells, carry no such risk for the formation of teratomas. These facts are well known and well understood throughout the scientific community, and always have been, although they are not often reported to the general public by the media.

The three companies under current scrutinization, namely, Geron, Advanced Cell Technology, and Novocell, are in the process of planning their imminent clinical trials to test embryonic stem cells in the treatment of, respectively, acute spinal cord injury, visual impairment, and diabetes. Following the announcement by the FDA, yesterday’s discussion among a panel of experts focused on the many unanswered questions that are associated with the as yet unproven safety and efficacy of embryonic stem cells.

Ever since 1999, when an 18-year-old patient named Jesse Gelsinger died four days after receiving experimental gene therapy in a clinical trial, FDA regulators have been particularly sensitive to potential risks that may be associated with clinical trials, and justifiably so. Any further undesirable medical conditions that may result from clinical trials would not only constitute personal tragedies for the individuals involved, but such consequences would also constitute severe policy setbacks for the entire FDA approval process as a whole. Currently, with human embryonic stem cells, the dangers are already well documented and no successes to date have ever been reported or published. Thus far, human embryonic stem cells have never been used to treat any human disease or injury, precisely because human embryonic stem cells have proven to be so highly problematic in the laboratory. By dramatic contrast, however, adult stem cells are already being used in numerous clinics around the world to treat a wide variety of diseases and injuries, efficaciously and in most cases without any side effects.

According to the authors of this review, “Scientists know that undifferentiated stem cells can form a benign mass known as a teratoma when injected into animals, and they fear that a safety incident in the first round of clinical trials could devastate the already-troubled field. The cell therapies under development use differentiated cells, but the possibility remains that some undifferentiated cells may be left in the mix.” While teratomas are technically classified as “benign”, in the sense that they do not metastasize, they do have a malignant counterpart known as a teratocarcinoma, which may also form from embryonic stem cells. It should also be noted that a person can die from either of these tumorous forms, including the so-called “benign” teratoma.

The committee convened by the FDA plans to release a formal guidance statement, formulated at yesterday’s meeting. Meanwhile, however, the 3 companies under consideration remain undaunted, with Geron in particular insisting that they will proceed with plans for clinical trials with embryonic stem cells that will commence in the summer of this year.