脊髓损伤(SCI)修复困难，神经干细胞是治疗SCI患者的希望。神经生长因子(NGF)是干细胞分化必需的神经营养因子之一，具有较强的促分化和促增殖能力。本项目前期研究发现脂质体包载的NGF能调控自噬促进大鼠SCI修复，但是无法修复脊髓空洞，更无法及时根据缺氧微环境变化调控NGF的表达量。因此，在本课题组已经成功构建的低氧调控性NGF腺相关病毒载体的基础上，拟用基因转染技术获得可控性基因修饰神经干细胞体系。本项目拟将上述可控性基因修饰干细胞移植至大鼠急性SCI模型，通过低氧调控NGF表达，探讨可调控性基因修饰干细胞对SCI功能修复的影响，观察炎症反应、氧化应激、血管再生等微环境因素的变化；重点关注自噬在神经干细胞分化和促修复过程中的相关机制及其与NGF基因调控的联系，旨在为SCI研究提供新的治疗策略和深入的理论基础。

Spinal cord injury (SCI) has proven to be very difficult to repair. The neural stem cell is hope for the treatment of SCI patients. Nerve growth factor (NGF) is one of the essential neurotrophic factor for stem cells, and has the strong capability of differentiation and proliferation. This project prophase research found that liposomes packaging NGF can regulate autophagy to promote the restoration of SCI in rats, but it can't repair syringomyelia, nor it can regulate the expression level of NGF in the hypoxic microenvironment. Therefore, in this project, we have successfully built low oxygen controlled expression of NGF via adeno-associated virus vector to generate a genetically modified neural stem cell system. This project intends to employ the genetically modified stem cell transplantation to rat acute SCI model, through the hypoxia-regulated NGF expression, and to explore the effect of genetically modified stem cells on the repairing function of SCI. We aim to investigate the influence of inflammation, oxidative stress, the change of the micro environmental factors such as angiogenesis; and focus on autophagy in neural stem cells and the repair mechanisms as well as the role of hypoxia-regulated NGF in this process. Overall, we aim at providing a new treatment strategy for the study of the SCI and for in-depth theoretical basis.