骨髓基质神经干细胞联合法舒地尔多视角治疗AD的探索

项目名称： 骨髓基质神经干细胞联合法舒地尔多视角治疗AD的探索

项目编号： No.81471412

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： 尉杰忠

作者单位： 山西大同大学

项目金额： 70万元

中文摘要： 目前阿尔茨海默病（AD）的治疗仍令人失望，本课题应用Rho激酶抑制剂Fasudil的抗炎、促神经突触再生和动员神经干细胞的特征，探寻Fasudil和骨髓基质干细胞（MSCs）联合治疗AD的新途径：1）拟避开仍不清晰的致病机制，针对AD患者炎性反应、突触损害和神经变性的病理特征，利用Fasudil的上述特征，联合自体MSCs设计治疗实验性AD的方案。经静脉或鼻途径，最大限度达到MSCs和Fasudil作用叠加和功能互补；2）研究不同途径联合治疗对外周免疫炎症的调节，包括T细胞亚群调节、巨噬细胞极化、免疫原性形成以及外周免疫炎症反应与AD病理变化之间的关联；3）研究不同途径联合治疗对中枢细胞反应的影响，包括移植细胞脑内定位、与脑内宿主细胞的相互作用、对神经突触形成和内源性神经干细胞的影响。拟构建中枢立体多元的作用靶点，形成神经元保护和再生所必要的微环境，为联合治疗AD奠定理论和实验依据。

中文关键词： 阿尔茨海默病；骨髓基质干细胞；Rho激酶；神经干细胞；神经再生

英文摘要： Nowadays, the treatment of AD remains difficult. We establish new ways to explore combination therapy of Rho kinase inhibitor Fasudil and bone marrow stromal cells (MSCs) for AD by virtue of Fasudil that display anti-inflammation,synapse formation and mobilization of neural stem cells(NSCs): 1) To avoid pathogenic mechanism that is still not clear, we directly focus on basic pathological features of AD including inflammatory response, synaptic damage and neuronal degeneration. We design a combination therapy of AD model, that is, MSCs combine with Fasudil. At the same time, we will compare intravenous or nasal routes of MSCs administration, achieving a maximum overly and complementary effect of MSCs and Fasudil. 2) By combination therapy of different routes, we try to explore peripheral immunomodulation and inflammation responses, including regulation of T cell subsets, polarization of macrophage subsets, formation of immunogenicity and relationship between peripheral immune/inflammatory responses and AD pathology. 3) By combination therapy of different routes, we try to explore the improvement of central nervous system microenvironment, including brain localization of transplanted cells, interaction with host cells (microglia and astrocytes) in the brain, inflammatory microenvironment, synaptic formation and mobilization of endogenous NSCs. We attempt to pay close attention to multi-targets for the neuroprotection and neuroregeneration of AD, providing possible therapeutic strategies in future treatment of AD.

英文关键词： Alzheimer'disease;Bone marrow stromal cells;Rho kinase;Neural stem cells;Neuroregeneration