Adult Stem Cells From Fat Help Multiple Sclerosis Patients

Journal of Translational Medicine, April 24, 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.