The Prospect of Stem Cells as Multi-Faceted Purveyors of Immune Modulation, Repair and Regeneration in Multiple Sclerosis

Natalie      Payne; Christopher      Siatskas; Adele      Barnard; Claude      C.A. Bernard

doi:10.2174/157488811794480735

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is characterised by an autoimmune attack on components of the myelin sheath and axons leading to neurological disability. Although longapproved current treatments for MS have so far only targeted immune components of the disease in a non-specific manner, the efficacy of these immunomodulatory treatments is limited given that they are only immunosuppressive and / or immunoregulatory and do not prevent long-term disease progression. As such, there is a clear need for more effective therapies that are capable of targeting other aspects of the disease including neurodegeneration, demyelination and the underlying causes of the autoimmune state. Emerging data suggest that hematopoietic, mesenchymal and neural stem cells have the promise to restore self-tolerance, to provide in situ immunomodulation and neuroprotection as well as to promote regeneration. This review will summarise burgeoning experimental and clinical evidence supporting the application of these stem cell populations for the treatment of MS.

Keywords: Autoimmune disease, immunomodulation, multiple sclerosis, neuroprotection, regeneration, stem cell, central nervous system, neurodegeneration, demyelination, hematopoietic, mesenchymal, neural stem cells, self-tolerance, Autoimmune disease,, stem cel, neurodegenerative disease, B lymphocytes, oli-goclonal immunoglobulins, cerebrospinal fluid, mye-lin sheath, axons, oligodendrocyte pathol-ogy, experimental autoimmune, proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), encephalitogenic molecule, CD4+ T cells, macrophages, cytokines, phagocytosis, major histocompatibility complex, tyrosine kinase 2, CD58 locus, T regulatory cells, magnetic resonance imaging, glatiramer acetate (Copaxone), leukocyte, na-talizumab (Tysabri), mitoxantrone (Novantrone),, hematopoietic stem cells (HSC), mesenchymal stem cells (MSC), bone marrow transplan-tation (BMT), cyclophosphamide, gadolinium, brain atrophy, allogeneic, immunoablation, osteoblasts, multipotent progenitor cells, chondrocytes, adipocytes, murine, adipose tissue, tumor necrosis factor-alpha (TNF-), endodermal, ectodermal, immunocytochemical, hippocampus, microenvironment, xenogeneic, oligodendrocytes, chemokines, peripheral blood, myocardial infarction, neural precursor cells, platelet derived growth factor-, semaphorins, nerve growth, remyelina-tion, neurotro-phin 3