Expert Rev Neurother. 2011 Sep;11(9):1295-303. doi: 10.1586/ern.11.113.
Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis.
1Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montréal, QC, Canada.
Phase I clinical trials exploring the use of autologous mesenchymal stem cell (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number of centers across the world. MS is a complex and chronic immune-mediated and neurodegenerative disease influenced by genetic susceptibility and environmental risk factors. The ideal treatment for MS would involve both attenuation of detrimental inflammatory responses, and induction of a degree of tissue protection/regeneration within the CNS. Preclinical studies have demonstrated that both human-derived and murine-derived MSCs are able to improve outcomes in the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs ameliorate experimental autoimmune encephalomyelitis is being intensely investigated. One of the major mechanisms of action of MSC therapy is to inhibit various components of the immune system that contribute to tissue destruction. Emerging evidence now supports the idea that MSCs can access the CNS where they can provide protection against tissue damage, and may facilitate tissue regeneration through the production of growth factors. The prospect of cell-based therapy using MSCs has several advantages, including the relative ease with which they can be extracted from autologous bone marrow or adipose tissue and expanded in vitro to reach the purity and numbers required for transplantation, and the fact that MSC therapy has already been used in other human disease settings, such as graft-versus-host and cardiac disease, with initial reports indicating a good safety profile. This article will focus on the theoretical and practical issues relevant to considerations of MSC therapy in the context of MS.
Keywords: adipose tissue, bone marrow, experimental autoimmune encephalitis, immunomodulation, mesenchymal stem cell, multiple sclerosis, multipotent stromal cell, neuroprotection, T lymphocyte, transdifferentiation
J Neurol Sci. 2013 Oct 15;333(1-2):43-9. doi: 10.1016/j.jns.2012.12.009. Epub 2013 Jan 4.
Mesenchymal stem cell transplantation in multiple sclerosis.
1Mellen Center, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA.
Mesenchymal stem cells (MSCs) are pluripotent non-hematopoietic precursor cells that can be isolated from bone marrow and numerous other tissues, culture-expanded to purity, and induced to differentiate in vitro and in vivo into mesodermal derivatives. MSCs exhibit many phenotypic and functional similarities to pericytes. The immunomodulatory, tissue protective, and repair-promoting properties of MSCs demonstrated both in vitro and in animal models make them an attractive potential therapy for MS and other conditions characterized by inflammation and/or tissueinjury. Other potential advantages of MSCs as a therapeutic include the relative ease of culture expansion, relative immunoprivilege allowing allogeneic transplantation, and their ability to traffic from blood to areas of tissue allowing intravascular administration. The overall published experience with MSC transplantation in MS is modest, but several small case series and preliminary studies yielded promising results. Several groups, including us, recently initiated formal studies of autologous, culture-expanded, bone marrow-derived MSC transplantation in MS. Although there are several potential safety concerns, to date, the procedure has been well tolerated. Future studies that more definitively assess efficacy also will need to address several technical issues.
Keywords: BM; CNS; EAE; EDSS; Expanded Disability Status Scale; FBS; HGF; IBMIR; IFN; IL; IV; Immunomodulation; MOG; MRI; MS; MSC; Multiple sclerosis; Neuroprotection; Regeneration; Stem cell transplantation; TNFα; bone marrow; central nervous system; experimental autoimmune encephalomyelitis; fetal bovine serum; hMSC-CM; hepatocyte growth factor; human mesenchymal stem cell conditioned medium; instant blood-mediated inflammatory reaction; interferon; interleukin; intravenous; magnetic resonance imaging; mesenchymal stem cell; multiple sclerosis; myelin oligodendrocyte glycoprotein; tumor necrosis factor-alpha
J Transl Med. 2009 Apr 24;7:29. doi: 10.1186/1479-5876-7-29.
Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis.
1Medistem Inc, San Diego, CA, USA.
The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. 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 MSC. 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. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.