骨髓间充质干细胞与神经干细胞序贯移植修复脊髓损伤的作用及机制研究

项目名称： 骨髓间充质干细胞与神经干细胞序贯移植修复脊髓损伤的作用及机制研究

项目编号： No.81472088

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： 申才良

作者单位： 安徽医科大学

项目金额： 80万元

中文摘要： 脊髓损伤（SCI）治疗棘手，干细胞（SCs）移植为其展现了良好的前景。神经干细胞（NSCs）可直接分化为各类神经细胞，是极有前途的替代治疗细胞，但脊髓损伤的微环境严重影响了NSCs转归。间充质干细胞（MSCs）可调节SCI的免疫炎性反应并旁分泌细胞生长因子，改善微环境。我们前期研究证实MSCs有利于共同培养NSCs的转归，但在体内早期脊髓损伤因子BMPs可能影响NSCs的转归，据此我们推测先行MSCs移植，再行NSCs序贯移植，才能有助于协同效应的最大发挥！本实验将在体外观察BMPs对 NSCs与骨髓间充质干细胞（BMSCs）共同培养时转归的影响；建立脊髓损伤大鼠模型，分别经蛛网膜下腔和主动脉序贯移植，检测脊髓BMPs及细胞因子水平，观察血管形成、脊髓空洞、胶质疤痕的大小，NSCs转归及脊髓功能恢复情况；探索序贯移植的有效性和途径并阐明机制。这可能为SCs治疗SCI提供新的方法和途径。

中文关键词： 骨髓间充质干细胞；神经干细胞；序贯移植；脊髓损伤

英文摘要： Spinal cord injury (SCI) therapy is intractable, nervertheless stem cells (SCs) transplantation shows good prospects.Neural stem cells (NSCs) can differentiate into various types of neural cells and are very promising replacement therapy cells, but the microenvironment of injured spinal cord seriously impact on the survival, colonization and differentiation of NSCs.Mesenchymal stem cells (MSCs) can regulate the immune response of SCI and paracrine growth factors, improve microenvironment. Our previous study has demonstrated that MSCs were benifited to NSCs fate，however BMPs which is a kind of early spinal cord injury factors in vivo will obstruct the effect. We speculate that the first MSCs transplantation and sequential NSCs transplantation, have a good cooperative therapeutic effect on SCI! The experiments will observe NSCs fate when BMPs is added into co-culture system with bone marrow mesenchymal stem cells(BMSCs) and NSCs ;Meanwhile we will detect spinal cord levels of BMPs and cytokines,and observe blood vessel formation, syringomyelia, glial scar size, NSCs fate and the spinal cord function after establishing the rat model of respectively subarachnoid or artery sequential transplantation NSCs to treat SCI in vivo;We also explore sequential transplantation effectiveness and way of perfusion，and elucidate the mechanism. Those may provide several new methods for SCI therapy of SCs.

英文关键词： mesenchymal stem cell;neural stem cell;Sequential transplantation;spinal cord injury