胚胎干细胞来源感光细胞在变性视网膜中的整合机制及Muller细胞的影响

项目名称： 胚胎干细胞来源感光细胞在变性视网膜中的整合机制及Muller细胞的影响

项目编号： No.31271051

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 徐海伟

作者单位： 中国人民解放军第三军医大学

项目金额： 80万元

中文摘要： 视网膜是干细胞移植进行神经修复的理想器官.近来大量文献报道干细胞移植可缓解视网膜病变和重建视觉功能，临床研究也初步证实干细胞在视网膜变性疾病治疗中的安全性和短期效果，但对于干细胞能否在变性视网膜中分化为感光细胞并和受者神经元形成具有正常功能的突触联系、增生的Müller细胞对其有何影响？目前未见报道。我们前期研究发现植入海马的ES细胞来源神经元能和受者神经元形成具有典型结构和功能的突触联系，变性微环境对外源性和内源性干细胞的命运均有显著的影响，但尚不清楚其对植入干细胞分化命运和整合影响的机制和途径。本研究拟采用ChR2光基因修饰的人ES细胞植入RCS视网膜变性大鼠，双光子显微镜结合电生理和形态学技术实时精确刺激植入细胞，明确干细胞移植视网膜的整合机制及变性微环境中Müller细胞的影响及机制，研究结果可为阐明干细胞移植治疗视网膜变性疾病的细胞替代机制提供理论依据。

中文关键词： 干细胞；视网膜；移植；整合；微环境

英文摘要： Retina is an ideal organ for cell transplantation in neural regeneration. The recent development of stem cell technique demonstrated that the damaged vision can be relived and restored by cell transplantation.The safety and the short term therapeutic effect of grafted stem cell in the degenerative retina has been reported in most recent clinical trials. However, it has not been clarified whether the grafted stem cell correctly differentiated into photoreceptor and formed the functional synapse with the neural circuit of the recepient,nor the influence of over-activated Müller cells in the degenerative retina .Our previous study showed that the synapse with typical structure and function was formed between the grafted embryonic stem cell-derived neurons and the neurons of the recepient in the hippocampus. And the degenerative microenviroment in the central nervous system significantly impacted the fates of transplanted and endogenous stem cells, with the mechanisms of influences on the intergration of stem cells has not been clarified.In this study, we infected the human embryonic stem cells with optogenetic ChR2 and induced into neural precusor cells before transplanted into the degenerative retina of RCS rats. Under the two-photon microscopy, combined with the electrophysiological and morphological techniques,

英文关键词： stem cells；retina；transplantation；Intergration；microenviroment