组织干细胞的神经保护机理研究

项目名称： 组织干细胞的神经保护机理研究

项目编号： No.31200680

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 曹巍

作者单位： 中国科学院上海生命科学研究院

项目金额： 25万元

中文摘要： 组织干细胞已成为目前干细胞治疗神经退行性疾病的最佳选择之一，然而其具体的作用机制尚不明确。为切实接近临床应用，本项目以人源的组织干细胞为研究对象，将深入阐明人源组织干细胞在帕金森疾病中的神经保护机制。我们将通过人神经瘤母细胞系SH-Sy5y,人原代神经细胞和大鼠帕金森疾病模型，采用real time PCR、Western blot、腺病毒载体转染、RNA干扰等手段，从分子、细胞、组织以及动物整体水平等多方面探讨组织干细胞治疗帕金森病的作用机制，揭示组织干细胞与机体微环境的交互作用；明确其体内作用的靶细胞；深入探讨组织干细胞在抗神经炎症/氧化应激/神经细胞凋亡等方面的作用；通过细胞因子表达谱和代谢组学等检测和分析，探寻组织干细胞在治疗中发挥关键作用的细胞因子或代谢产物。本研究将为揭示组织干细胞的治疗机制奠定基础，为组织干细胞在神经退行性疾病的临床防治提供新的思路。

中文关键词： 间充质干细胞；帕金森氏病；氧化应激；吲哚胺2;3 - 双加氧酶；

英文摘要： Mesenchymal stem cells (MSCs) are considered one of the most promising candidates for cell-based therapies in various neurodegenerative diseases, including Parkinson's disease (PD). Despite advances in MSC transplantation that aim to prevent neurodegeneration and motor dysfunction of PD patients in preclinical trials, the exact mechanism of MSC therapy in PD have not yet been ascertained. The aim of this study was therefore to address the molecular mechanism underlying the neuroprotective properties of human MSCs transplanted in 6-OHDA-induced rat PD model. Our previous report showed that MSC-mediated immunosuppression occurrs through inflammatory cytokine-upregulation of iNOS/IDO and chemokines, suggesting that MSCs are able to response to inflammatory signals and exhibit the immunoregulatory properties. Prompted by this finding, we hypothesize that upon the influence by in vivo neuro-inflammatory microenvironment, MSCs exert their neuroprotective effect in PD model through certain secreted factor(s) or metabolite(s). We propose three specific procedures to prove this hypothesis using primary human neural cell models and the rat PD model. We will first investigate the interaction between transplanted MSCs and endogenous neural cells to identify the target cells of MSC function in vivo. Next, we will examine whe

英文关键词： Mesenchymal stem cells；Parkinson’s disease；Oxidative stress；IDO；