title: Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.
abstract: Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. 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. Active MSC-CM contained HGF, and exogenously supplied 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 lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.
authors.affiliation: Center for Translational Neuroscience, Department of Neurosciences, Case School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Bai
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lennon
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Caplan
authors.forename: Anne
authors.initials: A
authors.lastname: DeChant
authors.forename: Jordan
authors.initials: J
authors.lastname: Hecker
authors.forename: Janet
authors.initials: J
authors.lastname: Kranso
authors.forename: Anita
authors.initials: A
authors.lastname: Zaremba
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met