November 14, 2008 by

Business is Booming as Pfizer Targets the Aging Processs With New Adult Stem Cell Research

In a further sign of the increasing investment opportunities that are springing up throughout the stem cell industry, big pharma has now decided to capitalize upon stem cell research. According to Pfizer spokeswoman Ruth McKernan, the world’s largest drugmaker has allocated a budget of $100 million to be directed over the next five years toward developing stem cell products that will specifically target the treatment of diseases that are typically associated with aging, such as heart disease, diabetes, vision loss and hearing loss, among other ailments. While such stem cell research and development is already underway in smaller companies such as Geron and Novocell, this marks the first time that a major pharmaceutical organization has entered the field. Although its headquarters are in New York, Pfizer is dedicating its laboratories in Cambridge, Massachusetts and Cambridge, England to the development of drugs that will stimulate adult stem cells that already exist in the human body to heal injury and disease. According to Corey Goodman, president of Pfizer’s Biotherapeutics and Bioinnovation Center, the U.S. lab will focus on heart disease, cancer and diabetes, while the UK lab will research therapies for vision and hearing. Pfizer is planning to hire 70 new scientists by the end of 2009 to staff laboratories at the two locations. Although embryonic stem cells will constitute part of the research, the primary emphasis will be on stimulating the body’s own adult stem cells for self-repair, thereby slowing or possibly even reversing the aging process.

According to Alan Trounson, president of the California Institute of Regenerative Medicine, the state agency that funds stem cell research in California, “The major pharma companies are moving into the field and taking a very strong position. We feel they’re like big ships coming together with us. It’s starting to be an armada.”

Biotech companies have not been entirely immune to the recent global financial crisis, with Pfizer’s stock losing 28% this past year, most recently falling 45 cents, or 2.7%, in one day, to $16.28 where it settled at 4:15 p.m. yesterday on the New York Stock Exchange composite trading. Nevertheless, the decision to join the stem cell bandwagon offers Pfizer greater protection from economic vicissitudes than the company might otherwise enjoy.

Embryonic stem cells are believed to be capable, at least theoretically, of differentiating into all 210 cell types of the human body, although this has never actually been demonstrated. By contrast, each type of adult stem cell is more limited in its “potency”, but taken altogether, all the various types of adult stem cells can also differentiate into all 210 cell types of the human body. Additionally, adult stem cells have thus far proven to be safer and more effective than embryonic stem cells, since embryonic stem cells still remain extremely problematic in the laboratory and consequently have never advanced to the clinical stage. Purely as an area of scientific interest, however, if not yet as a candidate for clinical therapy, embryonic stem cells are attracting the curiosity of more and more pharmaceutical companies, who also recognize the more immediate benefits of adult stem cell therapies, and who are therefore allocating research funding to both fields. Indeed, other major drugmakers besides Pfizer are also taking an increasingly active interest in both types of stem cell research and technology. The Swiss pharmaceutical companies Novartis AG and Roch Holding AG, for example, as well as Johnson & Johnson of the United States, and the London-based company GlaxoSmithKline, which is the world’s second largest pharmaceutical company, second only to Pfizer, have all initiated new investments in or partnerships with other biotech companies that are developing stem cell therapies. In 2007 Novartis and Roche helped fund the Spanish company Cellerix in the use of adult stem cells from subcutaneous fat for the treatment of patients with rare skin disorders, while in July of this year Glaxo announced a four-year, $25 million stem cell project with Harvard University. Similarly, J&J’s venture capital arm took an equity interest in the U.S. company Tengion, which is growing various organs such as bladders from adult stem cells in the laboratory, and J&J also led a $25 million round of funding for Novocell, which is involved in researching possible diabetes therapies from embryonic stem cells. According to Reinhard Ambros, executive director of the Novartis Venture Fund which invests in corporations involved in the life sciences, “There will be more companies coming with good technologies that will raise more interest from venture capital people.” However, Pfizer is the first big pharma company to dedicate an entire program exclusively to stem cell research, as pointed out by John McNeish, the director of Pfizer’s Massachusetts division. According to Corey Goodman, in order to enter the stem cell field, Pfizer first underwent a major change in corporate policy which was subjected to detailed reassessment and authorization by CEO Jeffrey Kindler.

Pfizer’s approach to their new stem cell research project is based in large part upon the work of Dr. Sheng Ding of the Scripps Research Institute in California, who explains that, “People might not know that stem cells are everywhere in the body and play a role in disease. Awakening stem cells already present in the body might be very attractive for therapeutic intervention to achieve healing and repair.” In 2007, Dr. Ding cofounded the San Diego-based company Fate Therapeutics, which is collaborating with Pfizer in developing novel pharmaceutical agents that can activate and mobilize endogenous dormant adult stem cells already residing in the hearts and other organs of people, so that such stem cells will be triggered to repair tissue that is damaged by injury or disease. According to Dr. McNeish, “Most people and scientists do believe that cells will be medicines in the near future.” Dr. Brock Reeve, executive director of the Harvard Stem Cell Institute, adds, “Originally, pharma stayed away because of the timeline, knowing that [embryonic] stem cell-based therapies will be years down the road. Where things have changed in the last year is that we can now create cells of interest in particular diseases,” referring specifically to the newly developed laboratory technologies that have made the news headlines over the past year, such as the technique pioneered by Dr. Shinya Yamanaka of Kyoto University in which iPS (induced pluripotent stem) cells are created by reprogramming ordinary adult, non-stem cell, somatic cells to behave with a pluripotency seemingly equivalent to that of embryonic stem cells.

As more and more venture capital funding and for-profit companies enter the stem cell field, thereby adding to the diversification and competition of marketable products, stem cells are no longer limited to the realm of university laboratories and academia, but instead represent a growing industrial sector of the world’s stock markets.

Filed Under: Heart Disease, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
November 14, 2008 by

New Stem Cells Identified for Regenerating Liver Tissue

Researchers at the University of Pennsylvania School of Medicine have discovered a novel protein marker which identifies adult liver stem cells. Led by Dr. Linda Greenbaum, assistant professor of medicine in the Division of Gastroenterology, the scientists found that cells which express the marker can differentiate not only into liver tissue but also into the types of cells that line the bile duct. Known as FoxL1, the marker will allow for the isolation and expansion of these stem cells, which offer great hope for the treatment of patients who suffer from chronic liver disease. According to the American Liver Foundation, there are currently over 17,000 people in the U.S. alone who are on waiting lists for liver transplants, and who significantly outnumber donors.

As Dr. Greenbaum explains, “In a healthy liver, the proliferation of mature liver and bile-duct lining cells is sufficient to maintain the necessary size and function of the organ. This even works when the liver is confronted with mild and acute injury, but the situation changes when injury to the liver is chronic and severe.” In more severe cases, the chronically injured liver tissue transmits chemical signals which in turn stimulate the proliferation of stem cells which eventually differentiate into new liver cells, though not usually in adequate amounts for complete healing. The newly discovered dual-potential liver stem cells which express the FoxL1 protein, and which were successfully associated with new liver fibroblasts in two mouse models, could be isolated and expanded in the laboratory and administered to patients therapeutically.

According to Dr. Greenbaum, “At this point, we haven’t identified the molecular targets that are regulated by FoxL1 in the liver stem cell.” Nevertheless, she adds, “This work has significant implications for cell-replacement therapies of chronic liver disease in the future.”

Filed Under: News, Stem Cells, Uncategorized Tagged With:
November 14, 2008 by

Cardiovascular Disease Successfully Treated With Patients’ Own Adult Stem Cells

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

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

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

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

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

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

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

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
November 12, 2008 by

Therapeutic Immune Response Identified From Cancer Stem Cells

Researchers from the biotech company ImmunoCellular Therapeutics (IMUC), Ltd., have presented data demonstrating that an immunological response is generated against cancer stem cells that are derived from a specific type of brain cancer known as glioblastoma.

Some types of cancer have been found to develop from their own unique type of cancer “master” or stem cells, and now a new type of cancer therapy may be possible by targeting the destruction of these cancer stem cells.

The cell surface marker CD-133 is found to be present on many different types of cancer stem cells and is therefore an excellent target for ICT-121, which is the name of IMUC’s proprietary cancer stem cell vaccine and which is specifically designed to generate a T-cell response against CD-133. Cancer stem cells which are CD-133-positve are perpetually self-renewing and notoriously resistant to standard therapies such as chemotherapy and radiation. As such, these cancer stem cells are highly tumorigenic and metastatic. An immunotherapy such as ICT-121, which targets the cancer cells at their point of origin and source, namely, while they are still in their earliest and most primitive stage, may be effective in destroying the cancer cells and stopping their proliferative ability.

John Yu, M.D., founder, chairman of the board of IMUC, and co-inventor of the ICT-121 technology, presented the company’s data over the weekend at the International Society for the Biological Therapy of Cancer (iSBTC) Conference in San Diego. According to Dr. Yu,

Filed Under: News, Stem Cells, Uncategorized Tagged With:
November 12, 2008 by

Brain Tissue Formed From Monkey Teeth Stem Cells

Scientists at the Yerkes National Primate Research Center at Emory University in Atlanta have used stem cells derived from the dental pulp of monkeys to stimulate the generation of neural cells in an animal model. Such an achievement offers hope for people who are afflicted with diseases of the central nervous system, such as Parkinson’s and Hungtington’s diseases, among others, as well as for those people who suffer from spinal cord and traumatic brain injuries.

Anthony Chan, DVM, Ph.D., assistant professor of human genetics at Emory’s School of Medicine, led the experiments. Dr. Chan and his colleagues took stem cells which they had derived from the dental pulp of a tooth of a rhesus macque, and transplanted the stem cells into the hippocampal areas of the brains of mice. The stem cells were then found to stimulate the new growth of neurons and other types of specialized neural tissue.

According to Dr. Chan, “By showing that dental pulp stem cells are capable of stimulating the growth of neurons, our study demonstrates the specific therapeutic potential of dental pulp stem cells and the broader potential for adult stem cells. Being able to use your own stem cells for therapy would greatly decrease the risk of cell rejection that we now experience in transplant medicine.”

Dental pulp stem cells are readily and universally available, as anyone of any age may have his or her dental pulp stem cells isolated during a routine visit to the dentist, thereby allowing for a very convenient type of autologous (in which the donor and the recipient are the same person) stem cell therapy.

Filed Under: News, Stem Cells, Uncategorized Tagged With:
November 10, 2008 by

Opexa to Present Data on its Cellular Therapies for Autoimmune Diseases

The biotech company Opexa announced today that its president and CEO, Neil K. Warma, will deliver a corporate presentation of its patient-specific therapies that are targeted for the treatment of autoimmune diseases such as multiple sclerosis (MS) and diabetes. The presentation will be at Rodman & Renshaw’s 10th Annual Health Care Conference in New York City and will include an overview of the company’s ongoing development program for Tovaxin which is an individualized T-cell therapeutic vaccine that is being developed for the treatment of MS, and which recently yielded positive data from a Phase IIb clinical trial in which 150 patients participated in the multi-center, randomized, double blind, placebo controlled study for the treatment of the Relapsing-Remitting (RR) form of multiple sclerosis. Among other measurements, MRI scans showed statistically significant decreased lesions in those patients who had received Tovaxin.

Tovaxin, which requires only 5 subcutaneous injections per year, is an individualized T-cell therapeutic vaccine based upon attenuated patient-specific myelin-reactive T-cells against peptides of protein from myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein or combinations thereof. Tovaxin is manufactured in Opexa’s in-house cGMP facility.

Tovaxin’s dual mechanism of action combats the demyelination of the nerve fibers in the central nervous system, which is the underlying cause of MS. Clinical results have demonstrated that Tovaxin induces an immune response that depletes and regulates the circulating pathogenic myelin-reactive T-cells that are responsible for attacking the myelin sheath of nerve fibers. Additionally, Tovaxin also rebalances the systemic immune response by causing a shift from pathogenic inflammatory T-cells to anti-inflammatory T-cells.

Opexa Therapeutics is focused on the development and commercialization of patient-specific autologous (in which the donor and recipient are the same person) cellular therapies that are based upon proprietary T-cell and adult stem cell products for the treatment of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and diabetes. The Company holds the exclusive worldwide license for adult multipotent stem cells derived from mononuclear cells of peripheral blood, which allow large quantities of monocyte-derived stem cells to be produced efficiently for use in autologous therapy, thereby eliminating the risk of immune rejection. In addition to Tovaxin, the T-cell therapy for MS which is currently in Phase IIb clinical trials, Opexa is also in the preclinical development of another product for diabetes mellitus.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
November 10, 2008 by

FDA Grants Clearance for the First Clinical Study With Placental Stem Cells

Celgene Cellular Therapeutics (CCT), a wholly owned subsidiary of Celgene Corporation, announced today that the U.S. Food and Drug Administration (FDA) has approved the company’s investigational new drug application to initiate a clinical trial which will test PDA001, an immunomodulatory therapeutic agent that utilizes adult stem cells derived from human placental blood via a proprietary process. Phase I of the clinical process will begin in the U.S. by the end of 2008, in which a multi-center trial will test the therapy on patients with moderate-to-severe Crohn’s disease who have also been found to be refractory to oral corticosteroids such as prednisone and to the immune suppressants that are commonly prescribed for such conditions.

PDA001 is a proprietary placental-derived adult stem cell therapy which is scalable to traditional pharmaceutical levels and which has applications that include immunology, inflammation, hematology and oncology. CCT owns and has patented a variety of proprietary technologies that are directed to novel placental cell types and cell populations, including methods for collecting, processing and storing many types of stem cells from the placenta. PDA001 is the first product to be developed as a result of CCT’s expanding portfolio.

According to Dr. Lloyd F. Mayer, director of the Immunology Institute, professor of medicine and chief of the divisions of clinical immunology and gastroenterology at Mt. Sinai Hospital in New York City, “This first placental-derived stem cell clinical trial is of vital importance given the significant number of people suffering from this debilitating disease. With the positive results from in vivo biodistribution and safety studies, our hope is that PDA001 will suppress the atypical immune and inflammatory reactions involved in the pathogenesis of Crohn’s disease, thereby resulting in a decrease in symptoms and improved quality of life for patients.”

Currently nearly a million people in the U.S. alone suffer from Crohn’s disease, which is a chronic inflammatory condition of the gastrointestinal tract that can be fatal in extreme cases. In the past, conventional medical treatment has consisted of non-specific anti-inflammatory or immunosuppressive agents, none of which are reliably effective and most of which cause side effects which are intolerable in a high percentage of the patients.

According to Robert Hariri, M.D., Ph.D., who is also CEO of Celgene Cellular Therapeutics, “This is the first step in our program to initiate clinical evaluations in a range of indications including not only Crohn’s disease, but other serious inflammatory and autoimmune diseases, such as multiple sclerosis and rheumatological disorders as well. By creating a novel cell therapy from a readily available source that does not require human leukocyte antigen-matching, we are hopeful that we can treat a large number of patients with a variety of devastating diseases.”

Celgene Cellular Therapeutics (CCT) is an adult stem cell company the focus of which is the discovery and development of novel therapeutics based upon adult stem cells derived from human placental and umbilical cord blood. In particular, the human placenta-derived cell therapy known as PDA001 is a cellular immune modulatory agent comprised of a novel cell population that is expanded in culture after being derived from normal, healthy, full-term human placental tissue. PDA001 is known to be genetically stable, displaying a normal diploid chromosome count, normal karyotype and normal senescence after prolonged in vitro culture exposure. Additionally, PDA001 is capable of immunomodulation and has been found to suppress T-cell proliferation while exhibiting immunomodulatory effects on other cell types that are involved in the immune response such as T-cell subsets, macrophages and dendritic cells.

As the first ever to be conducted with placental-derived stem cells, these clinical trials not only represent a milestone in the treatment of Chron’s disease, but also in the therapeutic advancement and availability of this particularly versatile population of adult stem cells.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
November 5, 2008 by

Genzyme and Osiris Form Adult Stem Cell Mega-Partnership

The biotech companies Osiris Therapeutics and Genzyme announced their signing of a collaboration for the commercialization of two adult stem cell products. According to the agreement, Osiris will commercialize the proprietary products Prochymal and Chondrogen in the U.S. and Canada, while Genzyme will commercialize the products throughout the rest of the world. Genzyme will make an upfront payment of $130 million to Osiris in additon to milestone and royalty payments that are estimated to be worth approximately $1.3 billion. Prochymal and Chondrogen are therapies that use allogeneic (in which the donor and recipient are different people) adult mesenchymal stem cells derived from bone marrow. Both of the products are late-stage treatments for a wide variety of diseases.

Although Osiris developed the therapies, Genzyme will provide the financial support for further marketing and commercialization of the products. This strategic alliance will leverage the leadership position that Osiris enjoys in the development of novel adult stem cell therapies, as well as Genzyme’s regulatory and marketing infrastructure outside of the U.S. and its expertise in the commercialization of cell therapies.

Genzyme and Osiris are already strategic allies and this is not their first collaboration. In 2007, the two companies forged an alliance to develop Prochymal for acute radiation syndrome, which resulted in both companies being awarded a $224.7 million contract in January of 2008 by the U.S. Department of Defense to develop Prochymal for the treatment of radiation-induced medical conditions related to warfare and terrorism. Once Prochymal is approved by the FDA for such indications, the Pentagon will buy 20,000 doses at $10,000 each.

According to Dr. Henri A. Termeer, Genzyme’s chairman and CEO, “This partnership further strengthens Genzyme’s late-stage pipeline of products with the potential to support our growth beyond 2011. Osiris is the clear leader in stem cell technology, which holds the promise to transform standards of care in a number of therapeutic areas in which Genzyme already has a strong presence.”

Similarly, Dr. C. Randal Mills, president and CEO of Osiris, adds, “Today Genzyme and Osiris have forged a powerful partnership in the emerging field of stem cell therapy. This relationship greatly enhances our ability to effectively introduce this groundbreaking technology on a global basis.”

As stated by Edward Tenthoff, an analyst at Piper Jaffray & Co., the deal is the largest ever in the field of stem cell therapy. The stem cells under consideration are exclusively adult stem cells, which are derived from mature tissues instead of embryos. According to Tenthoff, “This is a huge validation. This is a major win for everyone involved.”

Osiris is an adult stem cell company which was founded in 1992 and went public in 2006. Yesterday the company’s stock gained 43 cents, or 2.8%, settling at $15.93 a share after the company announced a third-quarter profit of $5.3 million. Its products focus on the treatment of inflammatory, orthopedic and cardiovascular condtions. The company’s 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. Prochymal is 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 Chron’s disease, both of which are potentially fatal conditions. 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. Data from all clinical trials are expected in 2009. Prochymal has also been approved to begin phase II clinical trials as a treatment for the regeneration of cardiac tissue following myocardial infarction. Additionallly, 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.

Genzyme, the world’s largest maker of drugs for rare genetic disorders, is well known for commercializing first-in-class biotechnologies. Founded in 1981, today Genzyme has a staff of more than 10,000 employees around the globe, with revenues of $3.8 billion. In 2007 Genzyme was awarded the National Medal of Technology, which is the highest honor awarded by the President of the United States for technological innovation. In addition to its large orthopedic franchise, Genzyme’s products are focused on rare genetic disorders, kidney disease, cancer, transplant and immune disease, diagnostic testing, cardiovascular disease, neurodegenrative diseases, endocrinology and other medical specializations in which patient needs are not adequately met. Most recently, Genzyme has also begun developing Mozobil, a novel proprietary product which stimulates the mobilization of the body’s own endogenous stem cells. Genzyme’s latest agreement with Osiris marks a major expansion by Genzyme into the field of cell transplant therapies.

As novel proprietary late-stage adult stem cell treatments which have already been shown to control inflammation, to prevent scarring and to promote tissue regeneration, both Prochymal and Chondrogen have the potential to treat a vast range of diseases. The mutual collaborative development and commercialization of these two adult stem cell therapies, by two of the most prominent biotech industry leaders, signifies an important milestone not only in the histories of these two leading companies, but also in the maturation of the adult stem cell industry. As David Meeker, executive vice president for Genzyme, explains, “The technology has evolved to a point where we have a level of confidence where we’re willing to make the deal. We’ll be working on the clinical development going forward and preparing for commercial launch.”

The partnership involves stem cell therapies which consist exclusively of adult stem cells, not embryonic stem cells, since embryonic stem cells have proven to be highly problematic in the laboratory and have therefore never advanced to the clinical stage.

Filed Under: News, Osteoarthritis, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
October 30, 2008 by

New Study Demonstrates Important Role of Endogenous Stem Cells in Angiogenesis

Scientists in Nagoya, Japan have demonstrated the important role that endogenous adult stem cells play in angiogenesis, which is the formation of new blood vessels. The study was led by Dr. Kazuhisa Kondo, who showed that “adipose-derived regenerative cells” (ADRCs) mobilized endogenous progenitor cells to enhance angiogenesis in a mouse model of critical limb ischemia.

Previous animal studies and human clinical trials have demonstrated that neovascularization is inducible by exogenous stem cell transplantation into ischemic muscle, with one clinical trial also demonstrating that human patients with critical limb ischemia respond to exogenous adult stem cell therapy not only with an increased systemic production of chemokines but also with the mobilization of endogenous CD34 stem cells from their bone marrow. It remained unknown, however, whether the resulting angiogenesis was caused directly by differentiation of the exogenous adult stem cells into the newly formed endothelial cells, or indirectly by an interaction between the cytokines and the recipient muscle. A study conducted by Dr. Keith March in 2004 also demonstrated that angiogenesis is mediated via cytokine secretion, although the exact extent of this mediation remained to be determined. Now, Dr. Kondo and his colleagues have demonstrated that the neovascularization which they observed in a mouse model of critical limb ischemia was directly dependent upon the mobilization of endogenous progenitor cells from the bone marrow.

After isolating ADRCs from the adipose tissue of mice in which hind-limb ischemia had been induced, Dr. Kondo and his team then expanded the ADRCs and transplanted them back into the ischemic tissue of the mice. Those mice which received the ADRCs showed a greater laser Doppler blood perfusion index and a higher capillary density when compared to the control mice. Additionally, the ADRCs were also found to increase circulating progenitor cells through the chemokine SDF-1 (stromal cell derived factor). Additionally, the administration of the systemic antibody to SDF-1 by intraperitoneal injection resulted in a blocking of the mobilization and efficacy of the adipose stem cells to induce angiogenesiis, through a mechanism by which the anti-SDF-1 neutralizing antibody caused a reduction in the number of circulating endogenous progenitor cells. Such a discovery highlights the central role that SDF-1 plays in facilitating the mobilization of endogenous progenitor cells.

Dr. Kondo’s study has important practical implications, since most people are not eager to have holes drilled in their bones for the harvesting of autologous stem cells from bone marrow. By contrast, adipose-derived stem cells now present an alternative source to autologous stem cell therapy, since the derivation of stem cells from fat is simpler than that from bone marrow. In fact, several companies such as Cytori have patents on self-contained closed systems by which adipose mononuclear cells are quickly and easily purified at the point-of-care.

As Dr. Kondo’s study indicates, the dynamics of therapeutic angiogenesis involve complex chemical and molecular interactions between the transplanted exogenous populations and endogenous stem cell reserves. In the stimulation of angiogenesis, adipose-derived adult stem cells offer a promising therapeutic modality, especially as a treatment for severe ischemic disease. Additionally, the chemokine SDF-1 is now recognized as playing a fundamental role in mobilizing endogenous progenitor cells.

Dr. Kazuhisa Kondo and his colleagues are in the Department of Cardiology at the Nagoya University Graduate School of Medicine and the Department of Bioengineering Sciences at the Nagoya University Graduate School of Bioagricultural Sciences.

Filed Under: News, Stem Cells, Uncategorized Tagged With:
October 28, 2008 by

Adult Stem Cell Company to Begin Clinical Trials for Critical Limb Ischemia

The U.S. biotech company Harvest Technologies has received Investigational Device Exemption (IDE) from the Food and Drug Administration (FDA) to conduct the first randomized, double blind placebo controlled clinical trial in the U.S. in which autologous adult stem cells will be used to treat patients with end-stage critical limb ischemia (CLI).

CLI is the terminal stage of peripheral artery disease (PAD), for which the only treatment is usually amputation, which carries a high risk of mortality. Now, however, adult stem cells offer the possibility of a new form of treatment for CLI, by which the diseased tissue of the affected limb could be regenerated, thereby sparing the limb from amputation.

This “feasibility trial” will enroll 48 patients who are at extreme risk of amputation, having exhausted all surgical and procedural options and who will be treated with their own autologous (in which the donor and the recipient are the same person) adult stem cells derived from their own bone marrow and prepared with the company’s proprietary BMAC (Bone Marrow Aspirate Concentrate) System which is a point-of-care device that concentrates a patient’s own adult stem cells from their own bone marrow in approximately 15 minutes at the bedside. The stem cells will then be injected directly into the affected limb in an effort to induce angiogenesis (blood vessel formation) and thereby rescue the limb from the necessity of amputation.

Based in Plymouth, Massachusetts, Harvest Technologies is the first company to offer clinicians a simple and easy-to-use point-of-care method for concentrating and preparing stem and precursor cells from a small aspirate of autologous bone marrow in just 15 minutes through its BMAC bone graft applicators, which facilitate the premixing of bone graft materials with bone marrow aspirate concentrate. Unlike previous studies that have been conducted in which more complicated methods were used for processing and concetrating adult stem cells from a patient’s bone marrow, the BMAC graft delivery pack streamlines and expedites both the preparation and the ultimate delivery of the graft composite to the surgical site.

Harvest Technologies is also providing a patient-education website for individuals participating in the clinical trial, and their referring physicians, at www.CLIclinicalstudy.com, where information on the study and the science underlying it is now available. The clinical trial is being led by Principal Investigator Mark D. Iafrati, M.D., Chief of Vascular Surgery at Tufts Medical Center in Boston, and the CLI study is also enrolling subjects at participating locations in South Carolina, Houston, Florida, and New York.

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