Judy DiCorcia of New York has written an open letter to President Obama in which she describes the improvement of her 10-year-old autistic daughter, Lauren, after adult stem cell therapy was administered to the child at the XCell-Center in Cologne, Germany.

The treatment, which cost approximately $10,000, took place in January of this year and consisted of a simple procedure in which adult stem cells were extracted from the girl’s own bone marrow and then readministered via a lumbar puncture in the girl’s spine. The technique was quick, simple and minimally invasive.

According to the girl’s mother, Lauren has shown significant improvement in a number of ways, including being able to sleep through the night for the first time in the girl’s life. Not quite half a year after the treatment, Ms. DiCorcia now reports that "Lauren is doing well. I would have to say that she plateaued at about the 12-week mark. Her situation is stable and fortunately all positive effects have persisted. I wish the doctor could fly to the U.S. and perform the therapy here!"

The XCell-Center is a private clinical group and institute for regenerative medicine which operates two treatment centers, one in Cologne and one in Dusseldorf, Germany. It is the first privately owned medical center in Europe to specialize in regenerative medicine. In addition to providing autologous adult stem cell therapies to patients, the XCell-Center is also actively involved in pre-clinical and clinical research. Since January of 2007, more than 1,600 patients have been treated with their own adult stem cells at the XCell-Center.

As stated on their website, the XCell-Center "is the first private institute worldwide to hold an official license for the extraction and approval of stem cell material for autologous treatment." Since only adult stem cells are used at the XCell-Center, not embryonic stem cells, the treatments are ethically noncontroversial and scientifically proven to be medically safe. Since only autologous (in which the donor and recipient are the same person) adult stem cells are used, there is no risk of immune rejection. The XCell-Center operates in full accordance with German law and European guidelines. The specialized team of physicians at the XCell-Center includes neurosurgeons, cardiologists, hematologists, orthopedists, radiologists and pharmacologists. In addition to autism, the XCell-Center also treats a number of other medical conditions which include stroke, cerebral palsy, spinal cord injuries, orthopedic injuries, ischemic heart disease, peripheral artery disease, diabetes and complications thereof, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and other degenerative illnesses.

The XCell-Center boasts an international advisory board and is a member of the German Society for Regenerative Medicine. Its headquarters are located at the Dominikus hospital in Dusseldorf, while its second branch is located at the Eduardus Hospital’s Institute of Regenerative Medicine in Cologne.

As explicitly stated on the website of the XCell-Center, "therapy with embryonic stem cells is strictly prohibited in Germany. At the XCell-Center, we only use the patient’s own stem cells for therapy." The strict prohibition of embryonic stem cell therapy in Germany, as in many other countries, is based not so much on ethical concerns but on concrete scientific reasons, not the least of which is the fact that embryonic stem cells are medically unsafe. In addition to causing teratomas (a specific type of tumor), embryonic stem cells are notorious for their numerous other inherent problems which disqualify them for any type of clinical therapeutic use.

Back in the U.S., Lauren’s mother, Ms. DiCorcia, wishes that this type of adult stem cell therapy were available in the U.S., so that she wouldn’t have to travel to Germany for her child’s treatment. Unfortunately, however, adult stem cell therapies, such as these that are being used with such success in Germany, which already exist and which are already being used in clinics around the world, would be available in the U.S. were it not for the fact that the FDA (Food and Drug Administration) has outlawed such therapies by designating each person’s own adult stem cells as a "drug" which therefore must be regulated by the same laws that apply to the giant pharmaceutical companies that manufacture prescription medication. Consequently, it is this stance by the FDA which is forcing all adult stem cell physicians to relocate outside of the U.S., where they set up their clinics in any and every other country on earth except the United States.

Ms. DiCorcia’s open letter to the President of the United States is reproduced herein:

"Dear President Obama,

I am the mother of a 10-year-old autistic daughter. In January, we took Lauren to Cologne, Germany for adult stem cell therapy. The center used her own stem cells drawn from her hip bone marrow, centrifuged the next day, and then reinserted via lumbar puncture the following day (2.95 million cells). Both procedures were quick and not invasive at all. In the past 6 weeks we have seen significant improvements in our daughter’s behaviors, focus, hyperactivity, and insomnia. I would rate a general improvement of about 40% – this is HUGE for a family living with autism. Our daughter started sleeping through the night for the first time (yes, she is 10 and got up every night) since stem cells. Lauren is happier just in her own skin – so much less frustrated and just generally happier. She is getting through her one-on-one therapy more quickly, better focused, and more compliant. Of course, it amazes me that this simple, non-controversial therapy cannot be done here in the United States.

Sincerely,

Judy DiCorcia"

The biotech company Pluristem Therapeutics, formerly known as Pluristem Life Systems, has been granted patent # 7,534,609 for a method of expanding undifferentiated hemopoietic stem cells.

Pluristem Therapeutics specializes in the development and commercialization of allogeneic (in which the donor and the recipient are not the same person) cellular therapy products derived from the human placenta for the treatment of severe ischemic autoimmune disorders such as multiple sclerosis, peripheral artery disease, ischemic stroke, inflammatory bowel disease including Crohn’s disease, and others. The company’s proprietary technology includes a 3D bioreactor, PluriX, which simulates the microenvironment of bone marrow substrates for the large-scale culturing and three-dimensional expansion of stromal cells without the need for supplemental growth factors or other exogenous materials. The cells generated by PluriX, known as "PLX" (PLacental eXpanded) cells, not only possess "immune privileged" properties but also immunomodulatory properties as well, and are expandable in vitro without exhibiting phenotypic or karyotypic changes. This new patent, however, was awarded to Pluristem for an invention involving methods and materials by which undifferentiated hemopoietic stem cells may be expanded in a novel type of bioreactor which is separate and distinct from the PluriX.

Pluristem Therapeutics is focused on the development and commercialization of off-the-shelf allogeneic cell-based therapies for the treatment of chronic degenerative ischemic and autoimmune disorders. As described on their website, Pluristem specializes in adherent stromal cells (ASCs) that are derived from the human placenta and which "are multipotent adult stem cells that have strong anti-inflammatory properties and can regenerate and repair damaged tissue." ASCs have already been shown to differentiate into nerve, bone, muscle, fat, tendon, ligament, cartilage and bone marrow stroma. Additionally, since they have low immunogenicity, ASCs do not require HLA (human leukocyte antigen) matching and are not at risk of being rejected by the patient’s immune system. After the ASCs are harvested from placental tissue, the cells are then expanded three-dimensionally into the PLX cells via the company’s proprietary PluriX 3D bioreactor, in which the cells are able to excrete their own cytokines and other immune modulators without the need for risky supplemental growth factors nor other exogenous materials. As adult stem cells that are derived from the human placenta, which is an extremely rich source of non-embryonic stem cells, ASCs are also ethically non-controversial in addition to being highly potent adult stem cells.

As stated on Pluristem’s website, "The Company has made a strategic decision to work only with adult stem cells since the practical use of embryonic stem cells is severely restricted by various religious, ethical and legal considerations."

In a manner which is similar to that by which the PluriX bioreactor three-dimensionally expands ASCs into PLX cells, the new invention allows undifferentiated hemopoietic cells to be expanded three-dimensionally upon stromal feeder cells, without undergoing differentiation. At least theoretically, such a bioreactor could be adapted to any type of cell, and a reviewer of the patent in StemCellPatents.com suggested the applicability of the bioreactor to the expansion of embryonic and iPS cells.

In separate though related news stories, earlier this year Pluristem received approval to begin clinical trials for the treatment of critical limb ischemia with its proprietary adult stem cell product PLX-PAD, an allogeneic placental-derived stromal cell product. In May of 2009, Pluristem also announced the selection of a major clinical site in North Carolina for the PLX-PAD Phase I clinical trial, which will be conducted at Duke University Medical Center. According to Zami Aberman, president and CEO of Pluristem, "We are very pleased to be working with Duke University Medical Center on the Phase I clinical trial using our PLX cells and believe that being involved with such a prestigious, reputable institution emphasizes the important therapeutic future for our mesenchymal-like stem cells."

According to Duke University cardiologist Dr. Robert Mitchell, the principal investigator for the PLX-PAD trial, "We look forward to collaborating with Pluristem in studying this interesting potential approach to dealing with limb ischemia. This is an oftentimes devastating disease and beginning the process of understanding the action of these cells in a Phase I clinical trial is an important step forward."

In the U.S. alone, it has been estimated that as many as 12 million people suffer from critical limb ischemia (CLI), an advanced form of peripheral artery disease (PAD) that is associated with high rates of morbidity and mortality, often resulting in amputation and frequent hospitalization. Although standard medical therapies are currently ineffective in treating CLI, the market value for an effective CLI therapy has been projected to be over $1 billion. For the first time, cell-based therapies such as Pluristem’s PLX-PAD offer a potentially safe and effective treatment of a life-threatening medical condition which previously has been incurable.

In addition to its cell-based therapy for CLI, Pluristem is currently developing other adult stem cell products for the treatment of other degenerative, malignant and autoimmune disorders. The company’s first product, PLX-BMT, was directed at improving the engraftment of hematopoietic stem cells derived from umbilical cord blood as an alternative to bone marrow transplantation.

Although the company’s most recent patent, for a method of expanding undifferentiated hemopoietic stem cells, was awarded on May 19, 2009, the patent application was originally filed on April 11, 2005, at which time the company was known as Pluristem Life Systems. On November 26 of 2007, however, corresponding to a reverse stock split and the designation of a new ticker symbol, the company also announced the official change of its name to Pluristem Therapeutics.

(Please see the related news article on this website, entitled, "Pluristem to Begin Adult Stem Cell Clinical Trials for Critical Limb Ischemia", dated January 13, 2009).

Acute vascular rejection (AVR) remains a serious complication of heart transplantation. When the immune suppressant cyclosporin A is administered to recipients in the C3H-to-BALB/c heterotopic cardiac transplant model, however, survival of the grafts has been extended to as long as 15 days, which is nearly twice as long as graft survival time in untreated patients. Now, Canadian researchers have demonstrated a method for preventing AVR altogether.

Led by Dr. Hao Wang of the London Health Sciences Centre in Ontario, Canada, the scientists used a bone graft from a third-party donor, in addition to cyclosporin A, for immune modulation of the antibody-mediated AVR. The results indicated indefinite allograft survival, for more than 100 days, without any signs of AVR.

The stem cells from the bone marrow were found to stimulate the generation of T regulatory cells as well as dendritic cells, which also resulted in radioresistance. By contrast, bone marrow mononuclear cells did not improve survival.

As the authors conclude, "Due to the fact that current immunosuppressive approaches are clinically ineffective at preventing AVR, this study provides promise for further investigations of BM (bone marrow) components as a means of addressing a currently unmet medical need."

Two of the authors of this study were also involved in a previous study published in April of this year in which adult stem cells derived from adipose (fat) tissue were found to exhibit immune modulation in three patients with multiple sclerosis.

While adult stem cells are most widely known for their ability to regenerate damaged tissue, their immunomodulatory properties also hold great therapeutic promise for a number of currently untreatable conditions.

(Please see the related news article on this website, entitled, "Adult Stem Cells From Fat Help Multiple Sclerosis Patients", dated April 24, 2009, as originally reported in the Journal of Translational Medicine).

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).

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.