Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis  

作　　者：Lianhua Bai Jordan Hecker Amber Kerstetter Robert H.Miller 

机构地区：[1]Department of Neurosciences,Center for Translational Neuroscience,Case Western Reserve University School ofMedicine [2]The Key Laboratory,Third Military Medical University Southwest Hospital

出　　处：《Neuroscience Bulletin》2013年第2期239-250,共12页神经科学通报（英文版）

基　　金：supported by NIH grants(NS 030800 and NS 077942) to RHM

摘　　要：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 MOG3~_~5-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 vivostudies 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.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 MOG3~_~5-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 vivostudies 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.

关 键 词：NG2 glycoprotein MYELIN oligodendro-cytes experimental autoimmune encephalomyelitis multiple sclerosis REMYELINATION 

分 类 号：R744.51[医药卫生—神经病学与精神病学]