间充质干细胞维持低免疫原性的机制研究

项目名称： 间充质干细胞维持低免疫原性的机制研究

项目编号： No.31200739

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 柳华

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 目前MSC移植免疫原性研究大多针对MSC能否引起免疫应答，以及促炎症因子对表面MHC表达的影响，而对MHC表达的调控机理尚未明确。课题组前期研究（J Cell Sci. 2012）及文献报道MSC的免疫原性可被诱导，在炎症因子作用下不同发育阶段的MSC被诱导后MHC表达程度有差异。未刺激状态MSC表面低表达或不表达MHC，但胞浆内可检测到大量MHC，意味着MHC的表面表达主要在翻译后受调控。因此本项目主要探索转运途径中关键因子对不同发育阶段MSC表面MHC表达的调控。该实验首先对不同发育阶段MSC的表面和胞浆内MHC以及重要转运相关因子表达初步分析，用RNAi技术建立体外MHC转运模型，探寻MHC转运的关键调控因子。该项目发现将揭示MHC的转运途径对MSC维持低免疫原性的重要作用，为促进MSC的移植存活、用于疾病治疗提供了实验基础和新思路。

中文关键词： 间充质干细胞；免疫原性；再生修复；主要组织相容性抗原；人白细胞抗原

英文摘要： Most current studies regarding the low immunogenicity of mesenchymal stem cells (MSC) focus on the induction possibility of immune response and the influence of proinflammatory factors on MHC expression. The mechanism of MHC expression onto MSC surface is unknown. Reports from the project applicant and other researchers showed that the immunogenicity of MSC and the surface expression of MHC could be induced by proinflammatory factors. There was difference of MHC expression among MSCs at different biological status. In spite of low or no expression of MHC on MSC surface, abundant MHC was detected in cytoplasm. It suggests that the surface expression of MHC is regulated at post-translation stage. Therefore, the purpose of this project is to investigate the effect of translocation-related molecules on surface expression of MHC by MSC, which are at different biological status. To achieve the purpose, this project will establish a MHC knock-down in vitro model for MHC translocation study via RNAi. A general expression profile of MHC and other translocation related molecules in MSC will be firstly analyzed. Then 1-2 important translocation related molecules will be further investigated by using the MHC knock-down model and functional assays. In summary, this project tries to explore the importance of MHC translocation

英文关键词： Mesenchymal stem cells；immunogenicity；regeneration；MHC；HLA