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Transplantation of Nurr1-overexpressing neural stem cells and microglia for treating parkinsonian rats.
CNS Neuroscience & Therapeutics ( IF 4.8 ) Pub Date : 2019-05-13 , DOI: 10.1111/cns.13149
Yuan Qian 1, 2 , Xiao-Xiang Chen 3, 4 , Wei Wang 2 , Jun-Jun Li 3 , Xian-Peng Wang 3 , Zhi-Wei Tang 3 , Jiao-Tian Xu 3 , Hai Lin 3 , Zhi-Yong Yang 3 , Li-Yan Li 5 , Xiao-Bin Song 3 , Jia-Zhi Guo 6 , Li-Gong Bian 7 , Lei Zhou 8 , Di Lu 6 , Xing-Li Deng 3
Affiliation  

BACKGROUND Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment. METHODS In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis. RESULTS The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months. CONCLUSIONS The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be a new potential strategy for the cell replacement therapy in PD.

中文翻译:

移植过度表达 Nurr1 的神经干细胞和小胶质细胞用于治疗帕金森病大鼠。

背景神经干细胞(NSC)移植被认为是治疗帕金森病的有前途的方法。但大多数神经干细胞分化为胶质细胞而不是神经元,并且由于炎症环境,只有少数神经干细胞在移植后存活。方法 在本研究中,将带有 Nurr1 基因的神经干细胞 (NSC) 和小胶质细胞移植到 PD 大鼠模型的纹状体中。通过逆转录聚合酶链反应(RT-PCR)、蛋白质印迹和免疫荧光分析评估结果。结果 Nurr1强制NSCs和小胶质细胞联合移植可改善PD大鼠的行为异常。与其他组相比,PD大鼠纹状体中酪氨酸羟化酶+细胞数量增多,Iba1+细胞数量减少。此外,5个月后PD大鼠纹状体中仍能检测到移植NSCs分化的多巴胺神经元。结论结果表明,移植Nurr1过表达的NSCs和小胶质细胞可以改善恶劣的宿主大脑环境,这将成为PD细胞替代治疗的新的潜在策略。
更新日期:2019-11-18
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