Beta-catenin/Wnt,DLL4/Notch 信号在外源NSCs和宿主NSCs及血管内皮祖细胞的动态变化及交互作用机制

In recent years, the basic and applied researches on neural stem cells (NSCs) transplantation for treatment of nervous system injury and disease, has been rapidly developed. Especially the clinical application study of NSCs transplantation in our country has been leading in the world. There are at least thousands of patients have received NSCs transplantation treatment (including the treatment cases of brain/spinal cord injuries and cerebral palsy which the author to take a variety migration path). Although the majority of cases have acquired certain effects, but that was still far away from the expectations of doctors and patients. The reason is mainly caused by our lack of knowledge about the mechanisms of the implanted NSCs growth, development, and differentiation, and interaction with the host cells (nerve cells and vascular endothelial cells) ; and rough, simple transplant method. This project intends to do with cell culture, immunohistochemistry fluorescent double labeling, Western blot, the nanoparticles live cell markers, to study the dynamic expressions of the "Beta-catenin/Wnt, Dll 4/Notch signaling pathway proteins" within exogenous NSCs and the host nerve tissue cells (endogenous NSCs, and endothelial progenitor cells) before and after transplantation, to explore the molecular mechanism of the interaction between the exogenous NSCs and the host nerve tissue cells. Which is wished to open new ideas for more effective clinical application of NSCs transplantation therapy, and to provide new scientific basis.

近年来，神经干细胞(NSCs)移植治疗神经系统损伤及疾病的基础与应用研究发展迅速，特别是NSCs移植的临床应用研究国内已走在世界前列，国内至少有上万例患者接受过NSCs移植治疗（包括作者采取多种移植途径对脑脊髓损伤、脑瘫的治疗），虽然大部分病例有一定效果，但与医患的期望还相距甚远。原因主要是对NSCs植入体内后的发育分化、及与宿主细胞（神经细胞及血管内皮细胞）间的作用机制认识不足，移植方法粗糙简单所造成。本课题拟通过细胞培养、免疫组织化学荧光双标、Western Blot、纳米微粒活细胞标记在体示踪等方法对"Beta-catenin/Wnt, Dll 4/Notch 信号通路蛋白分子"在外源NSCs和宿主神经组织（内源性NSCs、血管内皮祖细胞）移植前后动态表达的研究，探讨外源NSCs与宿主神经组织细胞间交互作用的分子机制，以期为临床更有效的应用NSCs移植治疗开启新的思路并提供科学依据。

本课题通过细胞培养、免疫组织化学荧光双标、Western Blot、纳米微粒活细胞标记在体示踪等方法，围绕着NSCs植入体内前后的发育分化、及与宿主细胞（神经细胞及血管内皮细胞）间的作用及“Beta-catenin/Wnt, Dll 4/Notch 信号通路蛋白分子”在外源NSCs和宿主神经组织（内源性NSCs、血管内皮祖细胞）移植前后动态表达的研究，探讨外源NSCs与宿主神经组织细胞间交互作用的分子机制。取得了一系列重要研究成果，在国内外期刊发表了一系列论文，被其他作者多次引用。