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

Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis.
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多发性硬化症小鼠模型中神经细胞移植介导的髓磷脂修复和功能恢复

DOI:
10.1007/s12264-013-1312-4
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发表时间:
2013-04
影响因子:
5.6
通讯作者:
Miller, Robert H.
Miller, Robert H.
中科院分区:
医学2区
文献类型:
--
作者:
Bai, Lianhua;Hecker, Jordan;Kerstetter, Amber;Miller, Robert H.

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细胞疗法正成为治疗诸如多发性硬化症(MS)等脱髓鞘疾病的主要焦点,因此确定促进髓磷脂修复的最有效细胞类型非常重要。若干组成部分有助于特定细胞类型的相对益处,包括细胞治疗的总体功效、治疗的可重复性、不同细胞类型的作用机制以及易于分离和产生治疗群体。一系列不同的细胞群促进MS动物模型的功能恢复,包括来自不同组织的神经干细胞和间充质干细胞。每种细胞群都有优点和缺点,并且可能通过不同的机制起作用。这种机制与成人中枢神经系统髓磷脂修复的相关性尚不清楚,因为治疗细胞通常来自发育中的动物。在这里,我们描述了从成人脊髓中分离和表征的神经细胞群,其特征是细胞表面糖蛋白NG2的表达。在功能研究中,将成年NG2+细胞注射到mog35 - 55诱导的实验性自身免疫性脑脊髓炎(EAE)小鼠体内,增强了中枢神经系统的髓鞘再生,而脊髓脱髓鞘区域的CD3+T细胞数量减少了约三倍。体内研究表明,在EAE中,NG2+细胞刺激内源性修复,而在体外,它们通过分化成少突胶质细胞来响应诱导炎症区域的信号。这些结果表明,成人NG2+细胞是促进多种不同疾病(包括脱髓鞘疾病,如多发性硬化症)神经修复的有用细胞群。
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 vivostudies indicated that in EAE, NG2+cells stimulated endogenous repair whilein vitrothey 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.
DOI: 10.1016/j.neuron.2010.09.009
发表时间: 2010-11-18
期刊: NEURON
影响因子: 16.2
作者:
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者: Bergles, Dwight E.
DOI: 10.1186/1742-2094-8-158
发表时间: 2011-11-13
影响因子: 9.3
作者:
Kucharova K;Chang Y;Boor A;Yong VW;Stallcup WB
通讯作者: Stallcup WB
DOI: 10.2217/imt.12.41
发表时间: 2012-05
期刊: Immunotherapy
影响因子: 2.8
作者:
Auletta JJ;Bartholomew AM;Maziarz RT;Deans RJ;Miller RH;Lazarus HM;Cohen JA
通讯作者: Cohen JA
DOI: 10.1038/nn.3109
发表时间: 2012-06
影响因子: 25
作者:
通讯作者: --
DOI: 10.1089/ten.teb.2008.0515
发表时间: 2009-06-01
影响因子: 6.4
作者:
Caplan, Arnold I.
通讯作者: Caplan, Arnold I.