帕金森病（PD）是一种严重影响人类健康的中枢神经系统退行性疾病。近年来，利用iPS细胞移植替代损失的多巴胺神经元，已成为医学研究的重要热点。本研究选用我国特有五指山小型猪作为实验动物，利用猪自身4种转录因子，同时组合使用基因替代性小分子化合物（如：VC6TFZ/VC6T）诱导猪胚胎成纤维细胞去分化为CiPSC-NSCs与CiPSC-DA 神经元前体，探析组合调控细胞重编程的表观遗传分子机理；通过与PD体外细胞模型共培养，分析其对PD细胞修复作用及互作机制；并尝试制备五指山猪急性损伤PD动物模型与慢性损伤模型，以CiPSC-NSCs-GFP+与CiPSC-DA前体-GFP+为移植供体，分别移植PD五指山小型猪黑质-纹状体，术后观察宿主运动能力恢复状况，对比观察供体细胞在宿主脑内的存活、分化多巴胺神经元及迁移情况，为组合诱导CiPSC-DA神经元前体移植治疗帕金森病和再生医学提供依据。

Parkinson's disease (PD) is a serious human central nervous system degenerative disease. In recent years, transplant of iPSCs to replace the loss of dopamine neurons, which has become the most suitable for PD treatment. In this study, we chose the wuzhishan miniature pig as experimental animals, and reprogramed the fetal pig fibroblasts to CiPSC derived NSCs-EGFP and CiPSC derived DA neural progenitor using a combination of pluripotent transcription factors and genes alternative small molecule compounds (such as: VC6TFZ/VC6T) under low oxygen conditions. Meanwhile, the epigenetic molecular mechanism of small molecule compounds and their combination control the reprogrammed cells would be evaluated; Through co-culture with PD cell model in vitro, the repair function and interaction mechanism of CiPSC derived NSCs-EGFP and CiPSC derived DA progenitors were analysized; The acute injury and chronic damage of PD wuzhishan miniature pig model were prepared by MPTP and 6-OHDA induction respectively. The CiPSC-derived NSCs-EGFP and CiPSC derived DA progenitors were transplanted into PD model nigra striatum, and normal NSC was served as control at the same time. Through exploring the DA differentiation, survival, migration, integration efficiency into the pig brain and synaptic connection between the host and the grafted cells, to evaluate the transplanting efficacy and choose the best transplanting donor and pathological animal model; And, to discuss the feasibility of the clinical application of CiPSC-derived NSCs-EGFP and CiPSC derived DA progenitors transplantation in the treatment of Parkinson's disease, and provide theoretical and practical basis, which could significantly promote the researches in this area.