miR-124基因修饰间充质干细胞治疗缺血缺氧性脑病的研究

项目名称： miR-124基因修饰间充质干细胞治疗缺血缺氧性脑病的研究

项目编号： No.81200950

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 刘华

作者单位： 山东大学

项目金额： 23万元

中文摘要： 间充质干细胞（MSCs）移植在治疗缺血缺氧性脑病（HIE）中具有良好的潜在应用价值。如何通过基因修饰促进MSCs在体内修复受损脑组织，促进功能恢复，目前已成为国内外学者研究的热点。我们的前期工作中首次发现，miR-124可促进脐带MSCs向神经样细胞分化。根据已有报道：抑制Notch信号通路可促进MSCs向神经细胞分化。本课题提出miR-124通过抑制Notch信号通路，促进MSCs向神经样细胞分化，从而发挥增强治疗HIE的作用。本课题拟以miR-124为研究对象，利用慢病毒表达载体、动物实验系统研究miR-124表达变化对MSCs向神经样细胞分化的调控机制，寻找miR-124调控的关键信号通路，明确miR-124修饰的MSCs在HIE的保护机制。该课题的完成将为MSCs向神经样细胞分化提供新的分子生物学机制，为HIE的治疗提供新的思路。

中文关键词： 间充质干细胞；神经干细胞；缺血缺氧性脑病；mir-124；诱导性多能干细胞

英文摘要： Using mesenchymal stem cells (MSCs) to treat hypoxic-ischemic encephalopathy (HIE),is the academic attention of a new strategy for treatment of nerve injury. The current focus of the field is how to using modified MSCs to improve neuroprotective effects. In our previous studies, we demonstrated miR-124 promoted differentiation of umbilical cord MSCs into neurons. Notch signaling is known to be involved in embryonic nervous system development and the regulation of MSC neuronal differentiation.Therefore,we propose that miR-124 promotes differentiation of MSCs into neurons by inhibiting the Notch signaling transduction pathway. To investigate this hypothesis , the expression of miR-124 will be firstly detected on the differentiation of MSCs to neuron-like cells in vitro by various induced methods in order to understand its effect on this process. In order to get miR-124 or miR-124 inhibitor gene modified MSCs, lentiviral vector are constructed which are recombined by miR-124 or miR-124 inhibitor gene to infect MSCs. By immunocytochemistry, RT-PCR and Western blot, neuron makers and Notch signaling pathway are detected to study the overexpression or inhibition of miR-124 on neuronal differentiation process. We also analyze the effect of miR-124 modified MSCs treatment in neonatal rat hypoxic-ischemic encephalopathy

英文关键词： Mesenchymal stem cells；neural stem cells；hypoxia-ischemia encephalopathy；mir-124；induced pluripotent stem cells