Lingo-1-fc修饰的iPS-NSC移植治疗自身免疫性脑脊髓炎的作用机制研究

多发硬化（MS）是由自身免疫反应引起的中枢神经系统炎性脱髓鞘疾病。目前对该病普遍采用的抗炎及免疫调节治疗不能改变中枢神经系统持续的功能性损伤且副作用严重。干细胞替代治疗该病一个可能的治疗途径。Lingo-1-fc作为lingo-1这一轴突髓鞘形成的负调控因子的拮抗剂，具有促进轴突生长和髓鞘再生，保护少突胶质细胞及神经元的作用。课题组前期研究结果表明Lingo-1-fc修饰的iPS-NSC移植具有更好的疾病治疗效果，因此，本研究以自身免疫性脑脊髓炎（EAE）为模型，将在分析Lingo-1-fc修饰的iPS-NSC移植治疗EAE效果的基础上，利用多种技术手段从移植干细胞的免疫调节、细胞替代、内源髓鞘再生等多方面探讨Lingo-1-fc修饰的iPS-NSC移植治疗EAE的作用机制，并评判其免疫调节、神经修复以及促进内源性髓鞘再生的多重治疗效果，为MS/EAE疾病新治疗手段的开发进行有益探索。

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) are autoimmune demyelinating disease of central nervous system (CNS) mediated by myelin-reactive CD4+ T cells. All the treatment currently used is anti-inflammation or immune regulation. These kinds of therapies can not recover the demyelination and neurodegeneration, but have serious side effects. Stem cells replacement therapy is considered a promising potential therapeutic method. Lingo-1-fc, an antagonist of Lingo-1, which is a negative regulator of axon myelin development, can promote axon growth and remyelination and protect neurons and oligodendrocytes from apoptosis. We have shown previously that lingo-1-fc modified iPS-NSC has better therapeutic effect on EAE treatment. In this project, based on analyzing the therapeutic effect of lingo-1-fc modified iPS-NSC on EAE, we propose to use different techniques to uncover the functional mechanisms of lingo-1-fc modified iPS-NSC transplantation for EAE treatment. We try to get the multiple therapeutic effects of this therapy: immune regulatory effect and neural cells replacement by iPS-NSC; in situ secreted Lingo-1-fc to promote endogenous remyelination. The results obtained by these experiments will provide a promising therapeutic method for MS/EAE.