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过表达 Nurr1 的神经干细胞和小胶质细胞移植治疗帕金森病大鼠。

Transplantation of Nurr1-overexpressing neural stem cells and microglia for treating parkinsonian rats.

机构信息

Yunnan Key Laboratory of Laboratory Medicine, Yunnan Engineering Technology Center of Digestive disease, 1st Affiliated Hospital of Kunming Medical University, Kunming, China.

Genetic Diagnosis Center, Women and Children Hospital, Kunming, China.

出版信息

CNS Neurosci Ther. 2020 Jan;26(1):55-65. doi: 10.1111/cns.13149. Epub 2019 May 13.

Abstract

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.

摘要

背景

神经干细胞(NSCs)移植被认为是治疗帕金森病的一种有前途的方法。但是,大多数 NSCs 分化为神经胶质细胞而不是神经元,并且由于炎症环境,只有少数 NSCs 在移植后存活。

方法

在这项研究中,将强制表达 Nurr1 基因的神经干细胞(NSCs)和小胶质细胞都移植到 PD 大鼠模型的纹状体中。通过逆转录聚合酶链反应(RT-PCR)、Western blot 和免疫荧光分析评估结果。

结果

联合移植强制表达 Nurr1 的 NSCs 和小胶质细胞可改善 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+细胞的数量增加,Iba1+细胞的数量减少。此外,在 PD 大鼠的纹状体中仍可检测到源自移植 NSCs 的多巴胺神经元。

结论

这些结果表明,移植过表达 Nurr1 的 NSCs 和小胶质细胞可以改善宿主大脑的不利环境,这将成为 PD 细胞替代治疗的新潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/184a/6930818/d7ec0932db74/CNS-26-55-g001.jpg

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