脊髓损伤分子病理机制及雪旺细胞联合骨髓间充质干细胞干预修复的研究

项目名称： 脊髓损伤分子病理机制及雪旺细胞联合骨髓间充质干细胞干预修复的研究

项目编号： No.81330042

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 冯世庆

作者单位： 天津医科大学

项目金额： 290万元

中文摘要： 脊髓损伤（SCI）发病率高、致残率高。其病理机制研究不清导致治疗困难。申请人团队长期致力于细胞移植修复脊髓损伤的研究，发现自体激活雪旺细胞（ASCs）不仅能分泌神经营养因子，抑制神经元凋亡，还可以诱导骨髓间充质干细胞（BMSCs）向神经元方向分化，促进轴突再生和功能恢复。但具体的激活及诱导机制尚不清楚。本研究拟建立脊髓损伤动物模型，通过microarray和iTRAQ蛋白质组学技术观察损伤前后miRNA和关键蛋白变化，探讨脊髓损伤的分子病理机制；揭示ASCs自我激活及诱导BMSCs向神经元方向分化的内在规律；根据损伤分子病理特点，分析不同时期自体ASCs联合BMSCs移植修复脊髓损伤的疗效及作用机理，明确脊髓损伤相关靶点及细胞信号通路，寻求建立更加可靠有效的细胞移植策略。同时自体移植避免伦理问题和免疫排斥反应，有利于突破我国干细胞领域的重大瓶颈，为实现脊髓损伤的有效修复和早期康复创造条件。

中文关键词： 脊髓损伤;病理机制;雪旺细胞;骨髓间充质干细胞;细胞移植

英文摘要： Spinal cord injury（SCI）is severe disease with high morbidity and high rate of disability. Because of the unknown pathological mechanisms, little progress has been made to the management of SCI. Our group has a long standing interest in the recovery of SCI based on the cell transplantation. Our previous research has shown that activated schwann cells (ASCs) not only can secrete neurotrophic factors to restrict the apoptosis of the neurons, but also induce bone mesenchymal stem cells（BMSCs）differentiate into neural cell which can promote axonal regeneration and functional recovery. However, the underlying mechanisms of activation and induction are still unclear. In this project, we plan to establish the animal model of SCI，and the changes of miRNA and key proteins after SCI will be examined through the technologies such as microarray and iTRAQ proteomics. The molecular mechanism of SCI will please be specific on this statement. Additionally, the mechanisms of ASCs self-activation and the regulation of the neural differentiation will be revealed. According to the pathological features of injury, the efficacy and repair mechanism of co-transplantation autologous ASCs and BMSCs in different time periods after SCI will be further investigated and defined. The goals of the project are to identify the targets and cell signaling pathways of SCI, and to establish a more reliable and effective treatment strategy of cell transplantation. The outcome of this proposal will shed light on fundamental problems confounding stem cell therapies and pave the way for the further research of spinal cord injury and improving early rehabilitation and efficacy of treatments.

英文关键词： spinal cord injury;pathological mechanism;schwann cells;bone mesenchymal stem cells;cell transplantation