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.

Adult Stem Cells Show Positive Results in a Pre-Clinical Study of Ischemic Stroke

In its second pre-clinical trial for the treatment of ischemic stroke, Pluristem Therapeutics Inc. has reported statistically significant results in both functional and anatomical improvement in an animal model after the use of one of its products which has been developed specifically for the treatment of stroke. Specializing in the commercialization of therapeutic products developed exclusively from adult mesenchymal stromal cells (MSCs) that are derived from the human placenta, Pluristem has developed a number of PLX (PLacental eXpanded) products, one of which, PLX-Stroke, is directly targeted for the treatment of ischemic stroke.

Using the widely accepted standard animal model for ischemic stroke, namely, hypertensive rats that had undergone middle cerebral arterial occlusion, the scientists systemically injected PLX-Stroke into some of the rats while other rats served as controls. In the rats that had received the PLX-Stroke, subsequent improvement was then observed both in functional paramaters such as the neurological severity scores and beam walking capability, as well as in anatomical parameters such as in the reduction of infarct size. The improvements were statistically significant when compared to the corresponding parameters in the control rats.

This pre-clinical study was conducted at the Fraunhofer Institute for Cell Therapy and Immunology in Leipzig, Germany, a branch of the Fraunhofer Society. According to Professor Frank Emmrich, who led the study, “PLX cells possibly show the potential to become a new treatment for the functional recovery from a stroke. The data show that a double injection of PLX cells at two different time points significantly improves the functional recovery and reduces the size of the lesion compared to the controls.” According to the President and CEO of Pluristem, Dr. Zami Aberman, “We are very excited about the results and believe that utilizing our PLX product may successfully treat millions of ischemic stroke patients and lead to a multi-billion dollar market. This independent study, together with the previously announced favorable pre-clinical results of PLX cells to treat limb ischemia and blood cancer, give us a robust pipeline for developing new therapeutic products.”

Approximately 90% of all strokes are ischemic, with the remaining 10% being hemorrhagic. Ischemic strokes are the result of an arterial occlusion in the brain, and it is estimated that approximately 2 million people per year throughout the world suffer ischemic strokes, many of whom either die or are rendered permanently disabled from the stroke. Now, adult stem cell studies such as these conducted by Pluristem offer a realistic and viable therapy which actually regenerates damaged neurological tissue.

An Adult Stem Cell Bill Advances in the Colorado State Legislature

Currently in the state of Colorado, there are only three hospitals in which the systematic collection of umbilical cord blood is routinely performed after the delivery of babies. In all the rest of the hospitals throughout the state, as in most other states, this precious source of pluripotent stem cells is discarded as waste. Democratic House Representative Dianne Primavera sees this as “an opportunity to turn medical waste into a medical miracle.” Indeed, patients such as Sheila Gannon agree. Diagnosed with advanced leukemia over two years ago, Sheila received an adult stem cell transplant from donated umbilical cord blood. As she stated in her testimony before the State House Health and Human Services Committee, “We are extremely grateful for this technology and for the medical community that administers it. I often think about the moms who graciously donate their umbilical cord blood. There is no doubt that without this I would not be here today.”

Many others enthusiastic advocates joined Representative Primavera and Ms. Gannon in supporting what is known as House Bill 1372, which, if ratified, would create the Adult Stem Cell Cure Fund: a voluntary income tax checkoff that would appear on future state income tax forms, revenue from which would promote the proper collection and storage of umbilical cord blood throughout the state of Colorado.

As Representative Primavera described, she sees an analogy between the umbilical cord as a “lifeline for a baby” and a lifeline for someone with a disease such as cancer or multiple sclerosis. As Sheila Gannon added, “I cannot think of a better way to pay it forward than to give all women the opportunity to donate the baby’s umbilical cord blood.” Doctors testifying before the Committee stated that there are roughly 80,000 births each year in Colorado, less than 1% of which currently result in a cord blood donation. If House Bill 1372 is passed, it is hoped that the money raised by the income tax checkoff could be used both for promoting education on the topic as well as for the actual cryogenic storage of donated cord blood, possibly for as long as 20 years for each donation. According to Dr. Chris Carey, who runs the OB-Gyn department at the Denver Health Medical Center, “It is my belief that this bill offers a tremendous opportunity to improve the health of Coloradans for a relatively small expense.”

Thus far, the new measure has passed the Committee unanimously. Next, it advances to the House Appropriations Committee.

Alzheimer’s Slowed by Stem Cells From Umbilical Cord Blood

More than 5 million people in the U.S. alone are currently afflicted with Alzheimer’s disease, and the global number is increasing dramatically each year. Now, researchers at the University of South Florida, in collaboration with Saneron CCEL Therapeutics, Inc., an affiliate of Cryo-Cell International, have demonstrated the ability of cord blood stem cells to slow the progression of this debilitating disease.

In this study, mice with symptoms mimicking those of Alzheimer’s were treated with a series of infusions containing stem cells derived from umbilical cord blood. The scientists then tested the mice for the two main markers of Alzheimer’s, and found that the myloid-beta proteins had been reduced by 62%, and cerebral amyloid angiopathy had been reduced by 86%. Currently, Alzheimer’s disease is considered to be irreversible since an effective conventional medical therapy does not exist. This study, however, demonstrates that Alzheimer’s disease can in fact be reversed with the potency of certain types of adult stem cells such as those derived from umbilical cord blood.

Although conservative groups often promote the use of adult stem cells over embryonic stem cells for ethical reasons, scientists are increasingly turning to adult stem cells over embryonic stem cells purely for scientific reasons. Increasingly, studies such as this indicate significant success with adult stem cells while embryonic stem cells still remain plagued with numerous unsolved scientific problems. According to Mercedes Walton, Chairman and CEO of Cryo-Cell International, an organization of cord blood banks which funded the study, “The scientific community has only skimmed the surface in uncovering the many potential therapeutic uses for cord blood stem cells, and this new research in Alzheimer’s disease may pave the way for discoveries around the use of these cells for a host of neurodegenerative and other chronic conditions.”

According to Dr. Jennifer Roback Morse, a senior fellow in economics at the Acton Institute for the Study of Religion and Liberty, “The use of umbilical cord blood is more humane than the use of embryos for two reasons. First, no human life has to be destroyed to produce the umbilical cord blood. Second, the use of umbilical cord blood will undoubtedly be less costly than the use of embryonic stem cells. The supply of umbilical cords is pretty much umlimited.”

Ever since 2004 when a South Korean woman who had been paralyzed for 20 years was able to walk again following cord blood stem cell therapy which repaired the damaged tissue in her spine, this particular source of adult stem cells has been a topic of of intense interest by numerous researchers and clinicians around the world. According to Cryo-Cell, cord blood offers one of the most viable sources of stem cells, as cord blood has already been used in over 7,000 transplantations since 1988, and stem cells derived from cord blood have been clinically administered to human patients for the treatment of more than 70 life-threatening illnesses, which include cardiac injury, neurological injury, type I diabetes, type II diabetes, leukemia, multiple sclerosis, and numerous other types of diseases and injuries.

Next, Alzheimer’s disease may also be added to the list.

Mesenchymal Stem Cells Discovered in the Eye

Mesenchymal stem cells (MSCs) are recognized as one of the most important types of stem cells, with one of the longest and most clinically advanced histories. Although bone marrow is the usual source from which MSCs are derived, they are also known to exist in many other types of tissue such as umbilical cord and placental blood, menstrual blood, peripheral blood, muscle and teeth.

Now researchers in India have discovered MSCs in the limbus of the human eye. After examining the epithelial cells of limbal tissue from patient biopsy samples collected during eye surgery, the scientists identified cells with a spindle-like morphology. The cells were then characterized for a number of parameters including morphology and immunophenotyping, and upon expansion in the laboratory the cells were found to possess a phenotype similar to that of MSCs that are derived from bone marrow. Most significantly, the cells were found to be capable ot differentiating into adipocytes (fat tissue) and osteocytes (bone and cartilage tissue).

Why would stem cells which are capable of differentiating into cartilage and bone exist in the eye? The answer to questions such as this may shed light not only upon the role that these cells play in limbal stem cell transplants but also on the role of MSCs in wound healing and regeneration in general. Especially in ocular injuries and surgeries, the identification of various subsets of stem cells in the human limbus that are similar to bone marrow-derived MSCs is particularly relevant. Already by 1999, a publication in the New England Journal of Medicine (Tsubota et al.) had reported 70 corneal epithelial stem cell transplants in which a statistically significant improvement in vision had been observed.

The presence of MSCs in the eye represents what the discoverers refer to as cells that are “unique to the adult stem cell niche.” Scientists are now investigating further the precise properties of these unique cells, for additional clues into the nature of molecular and cellular regenerative mechanisms.

Neuronal Tissue Created From Uterine Stem Cells Used in the Treatment of Parkinson’s Disease

At the 2008 annual meeting of the Society for Gynecologic Investigation (SGI), held this month in San Diego, California, researchers from the Yale School of Medicine reported improvement in mice with Parkinson’s disease who were treated with uterine stem cells. A debilitating neurodegenerative disorder, Parkinson’s disease is characterized by insufficient dopamine action in the motor cortex and basal ganglia regions of the brain. In this study, stem cells that were derived from human endometrial stromal cells were successfully cultured to differentiate into neurons, complete with the characteristic axon-like projections and pyramidal cell bodies. When the differentiated cells were then transferred into the brains of the mice with Parkinson’s disease, the researchers observed not only the growth of new brain cells, but also an increase in dopamine levels in the brains of the mice.

According to Hugh Taylor, M.D., professor in the Department of Obstetrics, Gynecology and Reproductive Sciences, and chief of Reproductive Endocrinology and Infertility at the Yale School of Medicine, “Now we have found that we can turn uterine stem cells into neurons that can boost dopamine levels and partially correct the problem of Parkinson’s disease. The implications of our findings are that women have a ready supply of stem cells that are easily obtained, are differentiable into other cell types, and have great potential for other purposes.”

The scientists were awarded the SGI President’s Presenter Award for their publication.