MSCs源exosomes负载α-突触核蛋白相关rno-miR-7对PD模型的联合作用研究

项目名称： MSCs源exosomes负载α-突触核蛋白相关rno-miR-7对PD模型的联合作用研究

项目编号： No.81471308

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘晶

作者单位： 大连医科大学

项目金额： 80万元

中文摘要： 近来干细胞分泌的细胞囊泡exosomes在神经损伤修复中的作用受到关注,而其来源于机体自然成分、良好的RNA转运能力及体液中稳定存在的特点,更显示出其在基因治疗中的巨大优势。项目拟发挥间充质干细胞（MSCs）源-exosomes作为干细胞信息携带者和基因治疗承载体的双重功能，以Thy-1 过表达帕金森病(PD)细胞模型及Thy-1 转基因PD动物模型为研究对象，从体内外综合研究MSCs源exosomes负载α-突触核蛋白相关rno-miR-7植入在PD治疗中的联合作用及机制。项目开辟了一个PD治疗的新理念，寻求到一条全新的治疗途径，通过探讨其可行性及技术可操作性，为今后发展PD联合治疗模式奠定基础理论及实验基础，具有重要的临床应用价值与社会意义。

中文关键词： 胞外体；间充质干细胞；帕金森氏病；基因治疗；小核糖核酸

英文摘要： The objective of the project is to investigate the potential co-application of stem cell transplantation and delivery gene therapy in the treatment of Parkinson's disease (PD) by introducing cellular transport vesicles-exosomes into PD model, since stem cell-derived exosomes can play dual function as stem cells information and gene therapy deliveries. The repair effects of exosomes secreted from mesenchymal stem cells (MSCs) of different sources on damaged nerve in PD model were firstly studied by parallel three-dimensional perfusion bioreactor and MSCs-derived exosomes with high repair ability was screened. Secondly, the technique of exosomes transfected with micro RNA was developed and MSCs-exosomes-miRNA complex was constructed. Our study have improved and developed the exosomes labeling technology by quantum dot to facilitate the long-term stable in vivo monitoring of exosomes. Then PD cell model with Thy-1 overexpression and Thy-1transgenic PD animal models were employed in the project to study the effects and mechanism of MSCs-exosomes-miRNA complexes on PD treatment in vivo and in vitro. We proposed for the first time a new attempt by intranasal administration of MSCs-exosomes-miRNA complex for PD therapy. The project also explored new ideas for PD therapy, using the micro RNA delivered by MSCs-derived exosomes and its mechanism. Our results may put forward new approaches to PD treatment by vesicle transport and gene-targeted delivery, which has significant clinical applications and social values.

英文关键词： exosomes;mesenchymal stem cells;Parkinson's disease;gene treatment;micro-RNA