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Multiple sclerosis (MS) is an autoimmune disease that results in progressive functional deficits. The initial course of disease is characterized by relapsing and remitting episodes that frequently progress to a more chronic functional loss. The target of immunological attack appears to be myelin sheaths, and loss of myelin death of myelinating oligodendrocytes leaves axons functionally compromised and vulnerable to damage. Most therapies for MS are directed toward suppression of the immune response. Cell-based therapies are emerging as an important approach to the treatment of multiple sclerosis On these researches in animal models of MS, treatment with Human Mesenchymal Stem cells (MSCs) results in functional improvement that reflects both modulation of the immune response and myelin repair. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC- stimulated recovery in EAE, neural cell development and remyelination. HGF promoted recovery in EAE, whereas cMet and antibodies to HGF Blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in Lysolechitin ? induced rat dorsal spinal cord lesions and in slice cultures. Together these data implicate HGF in mediating MSC-stimulated functional recovery in animal models of MS. These studies raise the possibility the HGF ? c Met pathway and HGF in mediating MSC may provide new therapeutic opportunities for the treatment multiple sclerosis. |
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