人诱导性多能干细胞源神经元移植治疗帕金森病的现状与未来

Application of human induced pluripotent stem cells-derived dopaminergic neurons in the Parkinson's disease models: present and future

背景:人诱导性多能干细胞源神经元的出现解决了胚胎干细胞来源的伦理学问题,为帕金森病移植提供了一个有前景的细胞替代资源。目的:总结人诱导性多能干细胞分化为多巴胺能神经元的诱导流程及其移植治疗帕金森病动物模型的应用进展。方法:以英文检索词"iP SC and Parkinson’s disease,induced pluripotent stem cells and Parkinson’s disease,ES cells and Parkinson,PD model,Parkinson and Lewy bodies"由第一作者检索1980至2015年Pub Med数据库,查阅近年诱导性多能干细胞源神经元移植治疗帕金森病的相关文献,最终保留40篇文献。结果与结论:文章综述了诱导性多能干细胞的不同来源,应用的各种诱导性多能干细胞的体外诱导分化方案,不同帕金森病模型的选择以及多位学者神经元移植试验的数据,详细呈现当前人诱导性多能干细胞源神经元移植治疗帕金森病的现状。根据路易小体的帕金森病机制来分析移植后路易小体的产生机制,为将来避免移植后路易小体的产生以及移植效果的优化提供了参考。优化的诱导性多能干细胞体外诱导分化条件可以明显改善帕金森病模型动物的行为学表现,结合影像学检测、免疫组织化学试验等检测手段可以更系统的评价移植效果。

BACKGROUND： The emergence of human induced pluripotent stem cells（i PSCs）-derived dopaminergic neurons solves the problem that the embryonic stem cell（ESC） shows an ethical issue on its source, providing a promising cell source for treatment of Parkinson＇s disease. OBJECTIVE： To summarize the differentiation methods of i PSCs-derived dopaminergic neurons in vitro, the choice of Parkinson＇s disease models and the transplantation of i PSCs-derived dopaminergic neurons in the Parkinson＇s disease treatment. METHODS： In order to search relevant articles about the application of i PSCs-derived dopaminergic neurons in the Parkinson＇s disease models from Pub Med databases（from 1980 to 2015）, a computer-based search was performed by the first author, using the key words of ＂i PSC and Parkinson＇s disease, induced pluripotent stem cells and Parkinson＇s disease, ES cells and Parkinson, PD model, Parkinson and Lewy bodies＂ in English. Finally 40 articles were chosen for further analysis. RESULTS AND CONCLUSION： Here, this paper is detailed to show the research status of human iP SCs-derived dopaminergic neurons for treating Parkinson＇s disease by reviewing the sources and in vitro differentiation schedules of i PSCs as well as the choice of Parkinson＇s disease models and outcomes of transplantation of i PSCs-derived dopaminergic neurons for Parkinson＇s disease treatment. According to the Parkinson＇s disease mechanism of the Lewy body, we analyze the generation mechanism of the Lewy body, providing references to avert the presence of Lewy bodies and optimize the outcomes of transplantation. The improvement of differentiation conditions of iP SCs can markedly improve the behavior outcomes, and moreover, we can systematically evaluate the outcomes of transplantation by iconography and immunohistochemical results.