间充质干细胞的自噬在其治疗脊髓损伤中的作用和分子机制研究

项目名称： 间充质干细胞的自噬在其治疗脊髓损伤中的作用和分子机制研究

项目编号： No.81471242

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： 徐锋

作者单位： 复旦大学

项目金额： 70万元

中文摘要： 脊髓损伤是临床常见的危重病，但目前缺乏有效的治疗方法。我们前期的研究表明，输注间充质干细胞（MSC）对脊髓损伤有一定的治疗作用，如果输注低血清培养的MSC可增强其对脊髓损伤的治疗效果。进一步研究表明，饥饿诱导的自噬增强了MSC治疗脊髓损伤的效应，但其机制未明。因此，本项目拟构建自噬增强/抑制的MSC，研究自噬作用对MSC的增殖/凋亡、迁移、分化、神经营养因子的分泌、免疫调节等生物学行为的影响及其信号转导改变；建立大鼠脊髓损伤模型，通过将自噬增强/抑制的MSC应用于脊髓损伤的治疗，研究MSC的自噬对其治疗脊髓损伤的影响和相应机制；进一步通过药物干预MSC的自噬及其相关信号通路证实自噬调控MSC治疗脊髓损伤的机制，从而在细胞、分子和动物水平上揭示自噬作用对MSC的生物学行为的影响以及调控其治疗脊髓损伤的分子机制，以期为脊髓损伤的干细胞移植治疗提供新思路和试验依据。

中文关键词： 脊髓损伤；间充质干细胞；自噬；Beclin；1

英文摘要： Spinal cord injury (SCI), a common clinical illness with high morbidity, causes an overwhelming burden individually and socially, and even worse, there is no well-established treatment for the trauma. Our preliminary studies showed that administration of mesenchymal stem cells (MSC) displayed somewhat effects, and still better if MSC were cultured with lower concentration of FBS, on improving SCI. Further research indicated that it was caused by starvation-induced autophagy, but the underlying mechanism remains to be clarified. Therefore,our study aims to study the influence on proliferation/apoptosis, migration, differentiation, secretion of neuronal growth factor, and immune regulation by autophagy through modifying autophagy in MSC. We also construct the rat animal model of spinal cord injury, on which we test the regulation of MSC by autophagy on the therapeutic effects on spinal cord and the mechanism. A further step will be rendered to confirm the mechanism by administration of autophagy inducers or specific signaling inhibitors. Thus, the project elucidates the impact of autophagy on biological behaviors of MSC and the underlying mechanism for regulation of its therapeutic effects on SCI, and helps us to manipulate the treatment of SCI. Hopefully the project provides a new perspective on MSC for therapeutic applications through modifying autophagy.

英文关键词： Spinal cord injury;Mesenchymal stem cell;Autophagy;Beclin 1