May 5, 2009 by

Stem Cells Return Lost Hearing

Researchers at the University of Sheffield have announced that they have differentiated fetal stem cells into the sensory hair cells of the ear, which could then be surgically inserted into the ear to restore lost hearing, at least theoretically.

According to Dr. Marcelo Rivolta, who led the study, "It will take several years before we are in a position to start doing human trials." He and his colleagues caution that the research is still in the preclinical, animal model phase, and has not yet advanced to a level where it could be performed safely and effectively in humans.

In the past, whenever auditory hair cells were damaged, permanent hearing loss would result since it was not possible to repair the damaged cells. Now, however, stem cells could be differentiated into auditory cells, thereby restoring lost hearing.

According to Dr. Ralph Holme, director of biomedical research at the Royal National Institute for Deaf People, which helped fund the research, "This research is incredibly promising and opens up exciting possibilities by bringing us closer to restoring hearing in the future."

Although the scientists used fetal stem cells, they are also investigating the ability of embryonic and adult stem cells to differentiate into auditory hair cells. Fetal stem cells have a number of inherent problems and risks, not the least of which is the formation of tumors. (Please see the related news article on this website, entitled "Fetal Stem Cell Therapy Could Prove Fatal", dated February 17, 2009). Presumably this is also the reason why iPS (induced pluripotent stem) cells were not differentiated into auditory neurons, which iPS cells are certainly capable of doing, but scientists have not yet been able to create a completely safe iPS cell which is free of cancer-causing genes and which also lacks the strong tendency to form teratomas (a type of tumor with cells and tissue from all 3 germ layers).

The auditory hair cells of the cochlea, or cochlear hair cells, function as the sensory receptors of both the auditory system and the vestibular system, not only in humans but in all vertebrates. In the past, damage to any part of the cochlear apparatus would often result in decreased hearing sensitivity, which was always considered to be irreversible. These fine hair cells are “bundled” in two sections, known as outer and inner hair cells, each of which performs a specialized function. The outer hair cells provide a purely mechanical amplification of sound, in a similar way as an acoustic preamplifier. The inner hair cells act as a more complex transducer, converting the mechanical vibrations into electrical signals that travel via the auditory nerve to both the auditory brainstem and the auditory cortex of the brain. Although the normal human hearing range is considered to be from 20 Hz to 20,000 Hz, some degree of sensorineural hearing loss is normal with advanced age.

Since all aspects of the auditory system were originally formed from stem cells, then at least in principle it should be possible to regenerate all aspects of the auditory system, given the right type of stem cell. At least conceptually, it should be possible to regenerate not only the auditory sensory receptors of the cochlear hair cells but also auditory neurons as well, regardless of where, exactly, the anatomical damage is located.

Filed Under: News, Stem Cells, Uncategorized Tagged With:
May 5, 2009 by

Pfizer and the University of Wisconsin Form Licensing Agreement

Once again, the pharmaceutical giant Pfizer has entered into a collaborative agreement with academia, this time licensing human embryonic stem cell patents from the University of Wisconsin at Madison. The patent technology will be developed not for clinical cell-based therapies, per se, but primarily for the testing of new drugs. Terms of the arrangement were made with the Wisconsin Alumni Research Foundation (WARF), the university’s licensing arm.

According to Ruth McKernan, chief scientific officer of Pfizer Regenerative Medicine, "Our license with WARF provides us with information and materials that will allow us to use their cell lines to explore a whole new range of therapies. Stem cells can be used to create specialized human tissue. Our scientists will determine how new medicines may be able to improve the way stem cells regenerate damaged tissues. We will be optimizing the production of cells that could, one day, be used for therapeutic purposes."

According to Wisconsin Governor Jim Doyle, "To have these two giants in the field of biopharmaceutical research and stem cell research come together brings us one step closer towards finding relief from diseases like diabetes, Alzheimer’s, Parkinson’s, multiple sclerosis and cancer."

Of course, the entire field of embryonic stem cell research was born at the University of Wisconsin at Madison, where Dr. James Thomson became the first person ever to isolate a stem cell in the laboratory, first from a nonhuman primate in 1995 and later from a human in 1998. By "these two giants", therefore, Governor Doyle is referring of course to Pfizer and also to the entire "industry" of stem cell scientists and laboratories that has sprung up around Dr. Thomson over the past decade.

Actually, as Dr. Thomson himself has stated on a number of occasions, he does not expect embryonic stem cells to yield cell-based therapies for diseases in the immediate future, but instead he expects embryonic stem cells to be most useful as a way of testing new pharmaceuticals, which in the past could only be tested in animal models since human tissue was not available. In fact, in November of last year, Dr. Thomson formed a new company, Cellular Dynamics International (CDI), precisely for this reason. Focused specifically on the commercialization of stem cell technology as it applies to drug testing and research, rather than to the discovery of cell-based therapies per se, CDI is centered around the development of new technology which can supply human heart cells to researchers for use in drug testing, especially for the testing of adverse reactions to pharmaceuticals. (Please see the related news article on this website entitled, "Embryologist and Stem Cell Pioneer Forms New Company", dated November 25, 2008, as originally reported in Forbes). In the past, side effects from drugs have been tested on animal cells, but rarely with great accuracy, with the result that physicians often prescribe medication to patients without knowing in advance whether or not an individual patient will have side effects to the medication, and then the patient is monitored to see whether or not side effects will occur. Dr. Thomson’s business model instead presents a different paradigm, in which adverse reactions to specific medications would be tested on human, not animal, cells, derived from the human embryonic stem cells, prior to prescribing a drug to a patient. As Dr. Thomson has explained in regard to CDI, "We’re very much going to be focused on products rather than long-term promises. There are things that drug companies want today."

Still, embryonic stem cells are, by their very nature, heterologous vis a vis any living individual, and therefore neither genetic nor immune matching is possible between the embryonic stem cells and the individual who is still alive and in need of the therapy, which thereby also eliminates the possibility of matching drug reactions. By sharp contrast, iPS (induced pluripotent stem) cells, which are derivable from any living person, offer matching not only of genetic and immune profiles but also of pharmaceutical reactions as well. In this regard, even Dr. Thomson has stated, "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."

As the world’s largest research-based pharmaceutical and biomedical company, Pfizer ranks number one in sales in the world, having reported $48.4 billion in revenue in 2007, from which the company invested $8.1 billion into their own research and development. In January of 2009, Pfizer announced its agreement to buy the pharmaceutical giant Wyeth for $68 billion. Pfizer was founded in 1849 and today employs approximately 81,900 people in more than 150 countries. Pfizer’s launched their Regenerative Medicine unit in November of 2008. (Please see the related news article on this website, entitled, "Business is Booming as Pfizer Targets the Aging Process With New Adult Stem Cell Research", dated November 14, 2008, as originally reported by Bloomberg Press).

Founded in 1848, the University of Wisconsin at Madison today has a staff of over 16,000 employees, more than 2,000 of whom are faculty, and a student body of just under 50,000.

(Please see the related news article on this website entitled, "Pfizer and University College London Form Licensing Agreement", dated April 29, 2009).

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
May 1, 2009 by

Patient Enrollment Beginning for Adult Stem Cell Trial

The Stem Cell Center at the Texas Heart Institute at St. Luke’s Episcopal Hospital in Houston has announced the commencement of FDA-approved Phase I clinical trials in which the Hospital is currently enrolling patients who have experienced any of three cardiovascular conditions, namely, a heart attack, heart failure or peripheral vascular disease. While patients will not be given monetary compensation for enrollment in the trials, they also will not be charged for any of the therapy or post-therapy monitoring that is conducted in relation to the trials.

The Stem Cell Center currently has several concomitant trials in which patients are being enrolled for heart failure. Qualifying patients must be on maximal medical therapy, exhibit a low ejection fraction, and have exhausted all conventional medical therapy such as bypass surgery and angioplasty. For the heart attack trials, qualifying patients must recently have been treated with angioplasty following a heart attack. For the peripheral vascular disease trials, in which adult stem cells will be injected directly into the affected areas of the leg, qualifying patients must exhibit claudication (blocked arteries in the legs) but no active infections in the leg, and must be refractive to conventional therapy.

Patients who wish to be considered for enrollment, and physicians who would like to refer a patient for consideration, should contact the Texas Heart Institute directly.

The Texas Heart Institute was founded in 1962 by the cardiac surgeon and pioneer, Dr. Denton Cooley, and today the Institute ranks as one of the largest cardiovascular centers in the world. As of 2008, doctors at the Texas Heart Institute had performed over 200,000 cardiac catheterizations, 100,000 open heart surgeries, and 1,000 heart transplants. Additionally, the Texas Heart Institute was one of only five centers selected by NIH (the National Institutes of Health) to study stem cell therapy as a treatment for cardiovascular disease, and the Stem Cell Center at the Texas Heart Institute was the first organization within the U.S. to receive FDA approval for a clinical trial in which advanced heart failure is treated with adult stem cells.

Filed Under: Heart Failure, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
April 29, 2009 by

Pfizer and University College London Form Licensing Agreement

Pfizer’s Regenerative Medicine division and the University College London (UCL) have announced the formation of a partnership for the development of stem cell-based therapies in the treatment of ophthalmic conditions. In particular, the collaboration will focus on the differentiation of human embryonic stem cells (hESCs) into retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration (AMD).

According to Dr. Ruth McKernan, chief scientific officer of Pfizer Regenerative Medicine, "We are excited to be working with pioneers in the field of stem cell ophthalmology from UCL. While we have much to learn about how [embryonic] stem cells can be used therapeutically, we are confident that this relationship will increase that understanding and help us advance to a time when our work may benefit patients worldwide."

Indeed, the world has everything yet to learn, about how, or if, embryonic stem cells could be used therapeutically, since thus far embryonic stem cells have never been used therapeutically, for anything. The only types of stem cells that have ever been used therapeutically are adult stem cells, which are already being used in clinics throughout the world for the treatment of a wide variety of diseases and injuries.

In fact, many scientists are already working on stem cell therapies for eye diseases which do not involve embryonic stem cells, but which instead involve either adult stem cells or iPS (induced pluripotent stem) cells, the latter of which are not naturally occurring stem cells, per se, but instead have been "induced", as the name implies, to exhibit a pluripotency that resembles that of embryonic stem cells. Just last month, for example, in April of 2009, it was reported in the Proceedings of the National Academy of Sciences that cells which had been isolated in the eye and which scientists had previously presumed, as early as 2000, to be retinal stem cells, are instead just ordinary adult stem cells, without any particular predilection toward differentiating into retinal cells. Such a discovery prompted a number of specialists within the ophthalmology field to turn their attention to the re-engineering of iPS cells as the best form of treatment for eye diseases, especially retinal diseases in which the light-sensitive photoreceptor cells degenerate, since these cells could be re-differentiated from iPS cells. Many other eye diseases also involve damage to the layer of ciliary epithelial cells that line the inside of the eye and which contains retinal cells, and iPS cells could be differentiated into these tissue types to treat such diseases. The search for a specific neural stem cell or retinal progenitor cell is therefore no longer as important as it was once thought to be, since iPS can perform the same function. Furthermore, since iPS cells can be developed from cells that are derived from a specific patient who has a specific disease, the iPS cells would already be genetically and immunologically matched to the patient, thereby eliminating any threat of immune rejection. Embryonic stem cells, by sharp contrast, are by their very nature a foreign, heterologous material which for which the obvious and predictable problems of immune rejection have yet to be resolved.

In reference to iPS cells, Dr. Michael Dyer, a member of the St. Jude Children’s Research Hospital Department of Developmental Neurobiology, explains, "This approach would solve many problems of developing cell-based therapy for blindness. First, these cells are immortal, so they can be grown indefinitely to produce large amounts of cells for treatment. And secondly, they would be immunologically matched to the patient, so there would be no danger of rejection. And thanks to some excellent research during the past 15 years, we know a lot about how to reprogram such stem cells to make them into photoreceptors."

Nevertheless, this new partnership between Pfizer and the University College London no doubt represents one of the largest of its kind. According to the terms of the agreement, Pfizer will provide an unspecified amount of funding to UCL, where research will be conducted on the differentiation of embryonic stem cells into retinal pigment epithelium cells, hopefully, for the development of therapeutic applications to both wet and dry age-related macular degeneration as well as other retinal diseases. Pfizer will retain exclusive worldwide rights to commercialize the therapies that result from the research, although it is unclear who exactly will retain the rights to related discoveries that cannot strictly be classified as ophthalmologic in nature.

Age-related macular degeneration affects more than half a million people in Britain alone. According to Professor Pete Coffey of the UCL’s Institute for Ophthalmology, who will direct the project, "We have not only the benefit of Pfizer’s experience of the regulatory process and their expertise in stem cell technology, but the ability, if this works, to produce on a much larger scale. It has huge implications, not only for our project, but for the field of regenerative medicine as a whole."

As the world’s largest research-based pharmaceutical and biomedical company, Pfizer ranks number one in sales in the world, having reported $48.4 billion in revenue in 2007, from which the company invested $8.1 billion into their own research and development. In January of 2009, Pfizer announced its agreement to buy the pharmaceutical giant Wyeth for $68 billion, thereby increasing the scope of its resources even further. Pfizer was founded in 1849 and today employs approximately 81,900 people in more than 150 countries. Pfizer’s launched their Regenerative Medicine unit in November of 2008. (Please see the related news article on this website, entitled, "Business is Booming as Pfizer Targets the Aging Process With New Adult Stem Cell Research", dated November 14, 2008, as originally reported by Bloomberg Press).

Located in central London, University College London was founded in 1826 and today boasts a staff of 8,000 and a student body of over 22,000.

(Please see the related news article on this website entitled, "Pfizer and the University of Wisconsin Form Licensing Agreement", dated May 5, 2009).

Filed Under: News, Stem Cells, Uncategorized Tagged With:
April 29, 2009 by

South Korea Conditionally Lifts Embryonic Stem Cell Research Ban

Still cautious almost exactly 3 years after the international fraud scandal involving Dr. Hwang Woo-suk, at which time human embryonic stem cell research was halted in South Korea, the country is slowly allowing a return to such research, provided that certain conditions are met.

The National Bioethics Committee has approved a request from scientists at Seoul’s Cha General Hospital to conduct human fetal stem cell research on aborted human fetuses, as long as the scientists meet the following 4 conditions: 1/ the scientists must secure written consent from the donors of the fetuses, 2/ the main focus of the hospital’s research must be conducted on laboratory animals, in an attempt to minimize research on human tissue, 3/ the hospital must establish an internal screening group to check for possible abuse, and 4/ the scientists must remove words and phrasing from the project title that would give people false hope. As an example of the fourth condition, the current title of the research project includes the phrase, "stem cell research which can cure diseases such as Parkinson’s", which should be changed, according to the conditions of the authorization.

As Dr. Roh Jae-kyung, chief of the National Bioethics Committee, explained to the scientists at Cha General Hospital, "This research that we have conditionally approved today is really just the very first step towards a new academic study. Though we hope this will eventually become a ray of hope for those patients with an incurable disease, we want you to refrain from premature or excessive expectations."

It was in May of 2006 that Dr. Hwang Woo-suk was indicted on embezzlement and violations of bioethics laws committed in 2005, after confessing to having falsified his claims that he had cloned the first human embryonic stem cells. As a result of the ensuing scandal, the South Korean government has been cautious not to allow such fiascos to happen again.

According to Dr. Chung Hyung-min, a leading researcher at Cha Hospital, "The decision will help reactivate stem cell research in South Korea. Stem cell research has been done by scientists in Britain and other countries. But there has been no successful case yet, using human eggs."

The Bioethics Committee has rejected a similar request from Dr. Hwang himself, who has also formally petitioned the Committee to be allowed to begin new human stem cell research from aborted human fetuses. Dr. Hwang is still on trial, however, for a number of charges that include fraud, embezzlement and ethical breaches.

(This article is a continuation of the story and related news article on this website, entitled, "South Korea Delays Decision on Cloning", dated February 7, 2009).

Filed Under: News, Stem Cells, Uncategorized Tagged With:
April 25, 2009 by

Cornell Conducts Adult Stem Cell Study on Horses

Researchers at the College of Veterinary Medicine at Cornell University in Ithaca, New York have reported the effective treatment with an autolgous adult stem cell therapy of tendonitis in horses.

Led by Dr. Alan J. Nixon, the study was not so much a "clinical trial" in the ordinary sense of the term, but was perhaps more correctly an "experimental study", since the researchers sacrificed the horses at the end of the evaluation period in order to conduct thorough histological and mechanical analysis of the tendons.

In the study, the researchers artificially induced tendonitis in the superficial digital flexor tendons (SDFT) of both forelimbs of an undisclosed number of horses. Six days later, autologous mesenchymal stem cells (MSCs) were then derived from the bone marrow of each horse, expanded and injected into one of the SDFT lesions, while the other untreated, "control" limb received an injection of 1 milliliter of saline. The MSCs were also gene-enhanced with IGF-1 (insulin-like growth factor 1), which has been demonstrated to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendonitis. Ultrasound examination of the tendons was performed at the start of the trial as well as at 2, 4, 6 and 8 weeks after administration of the therapy. According to an online abstract, "the horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics."

As Dr. Nixon explains, "The biochemical composition of the treated and untreated tendons were similar 8 weeks after treatment. However, tendons injected with the stem cells had significantly improved histology scores, indicating a more normal microscopic appearance in treated tendons than untreated tendons. Nonetheless, more research is needed regarding the optimal dose of stem cells and the use of gene enhancement techniques to augment the observed benefit before making this technology clinically available."

The researchers conclude, "These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendonitis."

The results of the trial will be published in an upcoming edition of the Journal of Orthopedic Research in an article entitled, "Mesenchymal stem cells and insulin-like growth factor-1 gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons."

Tendon injuries are often catastrophic and fatal in horses, while even minor tendon injuries can end the career of a race horse. According to Dr. Nixon, "At present, few successful treatment options exist for horses with tendon injuries. While stem cell therapy has become a hot topic in equine medicine, there are few controlled studies clearly documenting the safety or efficacy of this treatment modality for tendonitis in horses."

If killing the horse is a requirement for conducting a "controlled" study, then most people would probably conclude it’s a good thing that there aren’t many controlled studies that have been conducted.

In fact, a number of companies throughout the world are already treating horses, as well as other animals, with autolgous adult stem cell therapies, and not only do the animals improve as a result of the therapy but the animals are also allowed to continue living and enjoy the remainder of their lives. Perhaps the most renowned of these companies is the U.S.-based Vet-Stem, which has treated over 3,000 horses and 2,000 dogs with autologous adult stem cell therapy for a variety of joint injuries and degenerative conditions that include tendonitis as well as ligament injuries and age-related osteoarthritis. None of the animals treated by Vet-Stem’s autolgous adult stem cell therapy ever had to be euthanized, but instead were allowed to live out their natural lives.

Additrionally, 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 Vet-Stem founding CEO 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.

It is actually incorrect, therefore, to claim that "there are few controlled studies clearly documenting the safety or efficacy of this treatment modality for tendonitis in horses", since more than 3,000 case studies have been documented by Vet-Stem alone, not counting the other case studies conducted around the world by other companies that are performing similar therapies in other countries. It is also incorrect to claim that "more research is needed regarding the optimal dose of stem cells and the use of gene enhancement techniques to augment the observed benefit before making this technology clinically available", since, actually, such technology is, in fact, already clinicallly available.

Given the consistent success of such therapies as those used by Vet-Stem, one might seriously question the wisdom and necessity of conducting "controlled studies" in which the horses must be killed at the end of the study in order to determine the efficacy of the medical therapy. Horses are not generally bred and maintained in the same manner as laboratory mice, although in this Cornell study, one might easily get the impression that the two animals are interchangeable.

Ordinarily, veterinarians, like all physicians, measure the efficacy of a therapy by the ability of the patient to recover – not by killing the patient in order to examine the mechanical, biochemical and histological properties of the tissue that was treated. Such an approach to medical therapy would be considered entirely unacceptable in humans, and even in horses the concept seems to lack basic horse sense.

Filed Under: News, Osteoarthritis, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , ,
April 24, 2009 by

Adult Stem Cells From Fat Help Multiple Sclerosis Patients

An international team of researchers has reported improvement in three patients with multiple sclerosis (MS), all of whom received autologous adult stem cell therapy in which the stem cells were derived from each patient’s own adipose (fat) tissue.

Entitled, “Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis”, the publication appears today in the Journal of Translational Medicine. In the article, the scientists describe important properties of the “stromal vascular fraction” (SVF), which not only is rich in mesenchymal stem cells (MSCs) but also contains high concentrations of other beneficial constituents such as T-regulatory cells, endothelial precursor cells, preadipocytes, and a type of anti-inflammatory macrophage known as “alternatively activated” (M2) macrophage, which is a cell type with both anti-inflammatory and immunomodulatory properties. As the authors of the article explain, MSCs are already known to “produce numerous neurotrophic growth factors and inhibit pathological inflammation”, while “alternatively activated macrophages and T-regulatory cells are speculated to have the ability to modify the innate and adaptive immune responses”. One of the most important points of the paper, therefore, is not merely the potency of the adult stem cells – the MSCs – that were used, but also the degree to which immunomodulatory agents from the SVF are involved in the repair and healing processes. To be precise, therefore, the scientists who conducted the study are referring to the therapy as “SVF therapy”, rather than simply as “adult stem cell therapy”, since more components comprise the therapy than adult stem cells alone.

In MS, the two main conditions that contribute to the progression of the disease are the body’s autoimmune attack against the central nervous system, and the resulting demyelination. Currently, there is no standard medical treatment that can address either problem adequately, yet this study would seem to indicate that SVF therapy is capable of accomplishing both objectives, namely, SVF therapy seems to be capable of inhibiting the autoimmune attack against the central nervous system, and SVF therapy seems to remyelinate the demyelinated neurons.

In particular, the paper describes 3 patients with MS, all of whom went into remission following administration of the autologous, non-expanded, adipose-derived cells. Dr. Boris Minev, of the Moores Cancer Center and the Division of Neurosurgery in the Department of Medicine at the University of California at San Diego, is one of the leading investigators of the study. As Dr. Minev explains, , “All 3 patients in our study showed dramatic improvement in their condition after the course of SVF therapy. While obviously no conclusions in terms of therapeutic efficacy can be drawn from these reports, this first clinical use of fat stem cells for the treatment of MS supports further investigations into this very simple and easily-implementable treatment methodology. None of the presently available MS treatments selectively inhibit the immune attack against the nervous system, nor do they stimulate regeneration of previously damaged tissue. We’ve shown that SVF cells may fill this therapeutic gap.”

Significantly, one of the patients had suffered frequent and painful seizures (over 600 seizures) for three years prior to receiving the treatment, yet after receiving the SVF therapy his seizures stopped completely. He also reported a reduction in spasticity in his arms and legs as well as improved cognition. The second patient reported improved balance, coordination, mood and energy level following the therapy. Perhaps most dramatically, the third patient had first been diagnosed with MS over 15 years ago, in 1993, and within a matter of weeks after receiving the SVF therapy in 2008 he reported significant improvement in his balance, gait and coordination. According to Dr. Minev, “His condition continued to improve over the next few months and he is currently reporting a continuing improvement and ability to jog, run and even bicycle.”

The therapy consists of a very simple procedure which begins with a liposuction for removing cells from the patient’s adipose (fat) tissue, after which the cellular components of the fat are purified, in particular, the component known as the “stromal vascular fraction” (SVF). The purified SVF is then readministered to the patient intravenously. Such a simple procedure could be easily be conducted virtually anywhere. In fact, this very same liposuction procedure is already performed in thousands of plastic surgery clinics worldwide. A number of commercial entities are currently developing bench-top closed systems precisely for this type of autologous adipose cell therapy, such as the Celution system developed by Cytori Therapeutics and the TGI 1000 platform that is being developed by Tissue Genesis Inc., and both of which are currently entering clinical trials.

Adipose tissue is already known to contain a high concentration of adult stem cells, primarily mesenchymal stem cells (MSCs), in even larger quantities than bone marrow. MSCs are excellent candidates for an MS therapy for two main reasons, namely, 1/ MSCs have been shown in animal models to repair damaged neurons and to regenerate lost myelin, and 2/ MSCs suppress inflammatory reactions and produce different factors that slow inflammation. The SVF is thus a particularly robust form of therapy not merely for its rich abundance of MSCs but also because of its high concentrations of T-regulatory cells, which suppress autoimmunity, and also because of the large populations of the “alternatively activated” macrophage. In any type of MS therapy, it is absolutely essential not just to repair damaged neurological tissue but also to address the underlying mechanisms of autoimmunity through immune modulation. SVF appears to do both.

Autologous fat-derived MSC therapy has already been administered to over 3,500 horses and over 1,500 dogs for different types of inflammatory and autoimmune conditions as well as bone and joint injuries, without adverse side effects, thru the biotech company Vet-Stem, whose founder and CEO, Dr. Robert Harman, is one of the scientists involved in this MS study and one of the authors of this paper. As Dr. Minev adds, “Our collaborator in this publication, Dr. Robert Harman, CEO of Vet-Stem, has treated over 3,500 horses and 1,500 dogs with fat-derived stem cells for inflammatory conditions such as osteoarthritis immune-mediated polyarthritis. The current work is an excellent example of veterinary findings being translated into human medicine.”

In fact, as the authors point out in their abstract, “Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose-derived MSCs. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn’s fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported.”

Given the dramatic improvement achieved in all 3 MS patients, the authors of the paper conclude by proposing that larger, controlled trials be conducted.

According to Dr. Thomas Ichim, CEO of Medistem and one of the authors of the paper, “In addition to our endometrial regenerative cell (ERC) universal donor stem cell technology, for which an IND (investigational new drug appllication) has been filed, Medistem has been committed to developing a pipeline of therapeutic products, including in the area of immune modulation. Given our previous observations and IP (intellectual property) filings that a stem cell-rich component of adipose tissue, called the stromal vascular fraction, can concurrently immune-modulate while inducing regenerative activities, we are pleased to see the clinical translation of this approach into multiple sclerosis patients.”

Medistem Inc. is a biotechnology company founded to develop and commercialize technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company’s lead product, the endometrial regenerative cell (ERC), is a “universal donor” stem cell derived from menstrual blood that possesses the ability to differentiate into nine tissue types and produce large quantities of growth factors while exhibiting a large proliferative capacity. The company is currently focusing on the use of endometrial regenerative cells for the treatment of critical limb ischemia, an advanced form of peripheral artery disease that causes approximately 160,000 amputations in the U.S. per year.

The Journal of Translational Medicine is an open access journal of BioMed Central.

Filed Under: Adult Stem Cells, Multiple Sclerosis, News, Stem Cell Research, Stem Cells, Uncategorized Tagged With: , , , , , ,
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: , , , ,
« Previous Page
Next Page »