Roles of Stem Cells in the Treatment of Multiple Sclerosis

* Corresponding Author: Shahram Darabi Email:shahram2005d@yahoo.com Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system which is accompanied by demyelination of the nerves, axonal loss, and disability. The availability of multiple diseasemodifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in treating the disease. However, these drugs are only partially effective in preventing inflammatory tissue damage in the central nervous system and none of them directly promotes repair. The current treatments for MS largely comprise medications that are either immunomodulatory or immunosuppressive and are aimed at reducing the frequency and intensity of relapses. Recent studies have shown that cellular therapies are capable of repairing CNS neurons and can prevent inflammatory damage caused by the disease. Materials and Methods: A comprehensive review study was performed on MS, the etiologies, and treatment methods using the keywords including Stem Cells, Multiple Sclerosis, and Oligodendrocyte in valid medical databases, mainly PubMed. Among the collected papers, articles that were most relevant to the purposes of the study were selected and studied. Conclusion: Cell therapy is considered a promising potential treatment for multiple sclerosis, perhaps particularly for the progressive form of the disease for which there is currently no useful treatment. Stem cells can be differentiated into nerve cells, including oligodendrocytes, in the patient’s body and help repair neuronal myelin. Thus, in the present article, we reviewed a variety of cellular resources and their characteristics for the treatment of MS.

[1]  D. Pozo,et al.  Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study , 2018, PloS one.

[2]  Jeffrey A. Cohen,et al.  Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis , 2018, Multiple sclerosis.

[3]  B. Bunnell,et al.  Adipose stromal vascular fraction attenuates TH1 cell-mediated pathology in a model of multiple sclerosis , 2018, Journal of Neuroinflammation.

[4]  S. Hauser,et al.  B‐cell Therapy for Multiple Sclerosis: Entering an era , 2018, Annals of neurology.

[5]  Y. Liu,et al.  Umbilical cord mesenchymal stem cell transplantation in the treatment of multiple sclerosis. , 2018, American journal of translational research.

[6]  C. Oreja-Guevara,et al.  Inhibition of neurogenesis in a case of Marburg variant multiple sclerosis. , 2017, Multiple sclerosis and related disorders.

[7]  N. Scolding,et al.  Cell Therapy for Multiple Sclerosis , 2017, CNS Drugs.

[8]  Y. Zhang,et al.  Effect of Fingolimod on Neural Stem Cells: A Novel Mechanism and Broadened Application for Neural Repair. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[9]  M. Sadeghizadeh,et al.  Creatine Enhances Transdifferentiation of Bone Marrow Stromal Cell-Derived Neural Stem Cell Into GABAergic Neuron-Like Cells Characterized With Differential Gene Expression , 2016, Molecular Neurobiology.

[10]  G. Shroff Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease , 2016, The American journal of case reports.

[11]  T. Wehbe,et al.  Autologous Bone Marrow Derived Stem Cells for the Treatment of Multiple Sclerosis , 2016, International journal of stem cells.

[12]  K. Sawada,et al.  Functional Characterization of Acetylcholine Receptors Expressed in Human Neurons Differentiated from Hippocampal Neural Stem/Progenitor Cells , 2016, Journal of biomolecular screening.

[13]  M. Goldacre,et al.  Gender identity disorders and multiple sclerosis risk: A national record-linkage study , 2016, Multiple sclerosis.

[14]  H. Kazemi,et al.  Survival, proliferation and differentiation enhancement of neural stem cells cultured in three‐dimensional polyethylene glycol–RGD hydrogel with tenascin , 2016, Journal of tissue engineering and regenerative medicine.

[15]  J. Gimble,et al.  Human Adipose Stromal/Stem Cells from Obese Donors Show Reduced Efficacy in Halting Disease Progression in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis , 2016, Stem cells.

[16]  Daniel C. Lee,et al.  Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. , 2015, JAMA.

[17]  M. Ratajczak A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking , 2014, Leukemia.

[18]  A. Dulamea,et al.  Mesenchymal stem cells in multiple sclerosis - translation to clinical trials , 2015, Journal of medicine and life.

[19]  M. Soleimani,et al.  Comparison of in vivo immunomodulatory effects of intravenous and intraperitoneal administration of adipose-tissue mesenchymal stem cells in experimental autoimmune encephalomyelitis (EAE). , 2013, International immunopharmacology.

[20]  A. Hedayatpour,et al.  Promotion of Remyelination by Adipose Mesenchymal Stem Cell Transplantation in A Cuprizone Model of Multiple Sclerosis , 2013, Cell journal.

[21]  Hojjat Allah Abbaszadeh,et al.  Polarized neural stem cells derived from adult bone marrow stromal cells develop a rosette-like structure , 2013, In Vitro Cellular & Developmental Biology - Animal.

[22]  B. Trapp,et al.  Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR‐124 and reduced AMPA receptors , 2013, Annals of neurology.

[23]  H. Baharvand,et al.  Dibutyryl Cyclic AMP Inhibits the Progression of Experimental Autoimmune Encephalomyelitis and Potentiates Recruitment of Endogenous Neural Stem Cells , 2013, Journal of Molecular Neuroscience.

[24]  M. Sadeghizadeh,et al.  A new multistep induction protocol for the transdifferentiation of bone marrow stromal stem cells into GABAergic neuron-like cells. , 2013, Iranian biomedical journal.

[25]  C. Kerr,et al.  Immunomodulation by Transplanted Human Embryonic Stem Cell‐Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis , 2012, Stem cells.

[26]  M. Sahraian,et al.  Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study. , 2012, Current stem cell research & therapy.

[27]  L. Aigner,et al.  Adult mesenchymal stem cell therapy for myelin repair in multiple sclerosis. , 2012, Biological research.

[28]  E. Melamed,et al.  Transplantation of Placenta-Derived Mesenchymal Stem Cells in the EAE Mouse Model of MS , 2012, Journal of Molecular Neuroscience.

[29]  H. Coleman,et al.  Comparative Study on the Therapeutic Potential of Neurally Differentiated Stem Cells in a Mouse Model of Multiple Sclerosis , 2012, PloS one.

[30]  David H. Miller,et al.  Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study , 2012, The Lancet Neurology.

[31]  C. Schaumburg,et al.  Surgical Transplantation of Mouse Neural Stem Cells into the Spinal Cords of Mice Infected with Neurotropic Mouse Hepatitis Virus , 2011, Journal of visualized experiments : JoVE.

[32]  Herman Goossens,et al.  Clinical Potential of Intravenous Neural Stem Cell Delivery for Treatment of Neuroinflammatory Disease in Mice? , 2011, Cell transplantation.

[33]  G. Papadopoulos,et al.  Inflammatory changes induced by transplanted neural precursor cells in a multiple sclerosis model , 2011, Neuroreport.

[34]  P. Rameshwar,et al.  Stem cells and regenerative medicine: accomplishments to date and future promise. , 2010, Therapeutic delivery.

[35]  Jeff W M Bulte,et al.  Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. , 2010, Archives of neurology.

[36]  R. Mahfouz,et al.  Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: A pilot study , 2010, Journal of Neuroimmunology.

[37]  C. Kahn,et al.  Transplantation of adipose tissue and stem cells: role in metabolism and disease , 2010, Nature Reviews Endocrinology.

[38]  A. Sbarbati,et al.  Adipose‐Derived Mesenchymal Stem Cells Ameliorate Chronic Experimental Autoimmune Encephalomyelitis , 2009, Stem cells.

[39]  S. Miller,et al.  Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis , 2009, Glia.

[40]  J. de Vellis,et al.  Stem cell‐based cell therapy in neurological diseases: A review , 2009, Journal of neuroscience research.

[41]  B. Trapp,et al.  β4 Tubulin Identifies a Primitive Cell Source for Oligodendrocytes in the Mammalian Brain , 2009, The Journal of Neuroscience.

[42]  V. Yong,et al.  Continued disease activity in a patient with multiple sclerosis after allogeneic hematopoietic cell transplantation. , 2009, Archives of neurology.

[43]  J. García-Verdugo,et al.  Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. , 2008, Cell stem cell.

[44]  T. Ben-Hur,et al.  The changing face of neural stem cell therapy in neurologic diseases. , 2008, Archives of neurology.

[45]  M. Mostarica‐Stojković,et al.  Astrocytes stimulate interleukin‐17 and interferon‐γ production in vitro , 2007, Journal of neuroscience research.

[46]  A. Ghavamzadeh,et al.  Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. , 2007, Iranian journal of immunology : IJI.

[47]  R. D. Hatton,et al.  Interleukin 17–producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages , 2005, Nature Immunology.

[48]  G. Kraft,et al.  High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis. , 2003, Blood.

[49]  T. Olsson,et al.  Neural Stem Cells: A Potential Source for Remyelination in Neuroinflammatory Disease , 2003, Brain pathology.

[50]  E. Montserrat,et al.  CD34+ selected autologous peripheral blood stem cell transplantation for multiple sclerosis: report of toxicity and treatment results at one year of follow-up in 15 patients. , 2003, Haematologica.

[51]  Elena Cattaneo,et al.  Neural stem cell therapy for neurological diseases: dreams and reality , 2002, Nature Reviews Neuroscience.

[52]  J. Yagüe,et al.  MRI and CSF oligoclonal bands after autologous hematopoietic stem cell transplantation in MS , 2001, Neurology.

[53]  T. Holekamp,et al.  Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A. Anagnostopoulos,et al.  Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study , 1997, Bone Marrow Transplantation.