title: Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis.
abstract: Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis (MS), therefore it is important to identify the most effective cell types that promote myelin repair. Several components contribute to the relative benefits of specific cell types including the overall efficacy of the cell therapy, the reproducibility of treatment, the mechanisms of action of distinct cell types and the ease of isolation and generation of therapeutic populations. A range of distinct cell populations promote functional recovery in animal models of MS including neural stem cells and mesenchymal stem cells derived from different tissues. Each of these cell populations has advantages and disadvantages and likely works through distinct mechanisms. The relevance of such mechanisms to myelin repair in the adult central nervous system is unclear since the therapeutic cells are generally derived from developing animals. Here we describe the isolation and characterization of a population of neural cells from the adult spinal cord that are characterized by the expression of the cell surface glycoprotein NG2. In functional studies, injection of adult NG2(+) cells into mice with ongoing MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) enhanced remyelination in the CNS while the number of CD3(+) T cells in areas of spinal cord demyelination was reduced approximately three-fold. In vivo studies indicated that in EAE, NG2(+) cells stimulated endogenous repair while in vitro they responded to signals in areas of induced inflammation by differentiating into oligodendrocytes. These results suggested that adult NG2(+) cells represent a useful cell population for promoting neural repair in a variety of different conditions including demyelinating diseases such as MS.
authors.affiliation: Department of Neurosciences, Center for Translational Neuroscience, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. xiaohua42@hotmail.com
authors.forename: Lianhua
authors.initials: L
authors.lastname: Bai
authors.forename: Jordan
authors.initials: J
authors.lastname: Hecker
authors.forename: Amber
authors.initials: A
authors.lastname: Kerstetter
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D017690:Cell Transplantation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000276:immunology / Q000601:surgery*; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009474:Neurons / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000633:toxicity; D011509:Proteoglycans / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D001973:Bromodeoxyuridine; D017252:CD3 Complex; D017077:Culture Media, Conditioned; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011509:Proteoglycans; D020574:Proto-Oncogene Proteins c-sis; D000099216:Chondroitin Sulfate Proteoglycan 4; C047516:Plp1 protein, mouse; C485184:enhanced green fluorescent protein; C445081:myelin oligodendrocyte glycoprotein (35-55)