人脐带间充质干细胞诱导少突胶质祖细胞分化促进髓鞘再生的实验研究

项目名称： 人脐带间充质干细胞诱导少突胶质祖细胞分化促进髓鞘再生的实验研究

项目编号： No.81501028

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 卢正娟

作者单位： 南京大学

项目金额： 17.5万元

中文摘要： 多发性硬化是中枢神经系统慢性脱髓鞘疾病。促进髓鞘再生是缓解多发性硬化病理变化、减轻残疾的关键所在。我们的前期研究发现人脐带间充质干细胞（hUC-MSCs）移植对进展型多发性硬化有一定疗效；同时发现，hUC-MSCs对EAE鼠除了有免疫调节功能，还有促进髓鞘再生作用，并且该作用可能与抑制Lingo-1的水平有关。本课题基于前期工作的基础，采用实验性自身免疫性脑脊髓炎模型（EAE）、毒素模型（铜宗饲养）以及脑片培养，利用病理学和分子生物学等技术，进一步研究：1）hUC-MSCs促进髓鞘再生改善多发性硬化神经功能；2）hUC-MSCs通过诱导内源性少突胶质祖细胞（OPCs）分化促进髓鞘再生；3）hUC-MSCs激活RARs/RXRs通路抑制Lingo-1基因表达，促进髓鞘再生。我们期望通过阐明hUC-MSCs对多发性硬化治疗作用的可能分子机制，为hUC-MSCs的临床应用提供新依据。

中文关键词： 人脐带间充质干细胞；多发性硬化；少突胶质祖细胞；髓鞘再生

英文摘要： Multiple sclerosis (MS) is a chronic demyelinating disorder of the central nervous system (CNS) and a leading cause of disability in young adults. There is no effective treatment to prevent disease progression. Remyelination in MS is the key to alleviate the pathological changes and reduce disability. Our earlier research has shown that human umbilical cord mesenchymal stem cells (hUC-MSCs) therapy may be effective on progressive MS and Neuromyelitis optica; and we also found that in addition to immune modulation, hUC-MSCs might also promote remyelination in rats with experimental autoimmune encephalomyelitis(EAE), and the effect may be related to the inhibition of Lingo-1 level. On the basis of our earlier research, we perform this study with EAE model、toxic demyeliation model（Cuprizone diet）and brain slice culture to resolve the under questions: 1) hUC-MSCs alleviate neurological function by promoting remyelination; 2) hUC-MSCs promote remyelination by inducing endogenous oligodendrocyte precursor cells（OPCs）differentiation; 3）the molecular mechanism underlied hUC-MSCs promoting remyelation is activation of RARs/RXRs pathway which inhibits Lingo-1 gene expression. The results of this study will clarify the possible molecular mechanism of hUC-MSCs in the treatment of MS, providing new evidence for the clinical application of hUC-MSCs.

英文关键词： Human umbilical cord mesenchymal stem cells;multiple sclerosis;oligodendrocyte progenitor;remyelination