Therapeutic function of a novel rat induced pluripotent stem cell line in a 6-OHDA-induced rat model of Parkinson's disease

文献类型： 外文期刊

第一作者： Xu, Jiajia

作者： Xu, Jiajia;Li, Yangyang;Wu, Wenyu;Liu, Yumeng;Liu, Changqing;Ma, Caiyun;Zhu, Huan;Guo, Yu;Guan, Weijun;Ma, Caiyun;Liu, Changqing;Ma, Caiyun

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关键词： Parkinson's disease; rat induced pluripotent stem cells; cell reprogramming; neural transplantation; small molecules

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE （ 影响因子：5.314； 五年影响因子：4.892 ）

ISSN： 1107-3756

年卷期： 2022 年 50 卷 6 期

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收录情况： SCI

摘要： Parkinson's disease (PD) is a progressive neurodegenerative movement disorder of the central nervous system that results from the loss of dopaminergic (DA) nigral neurons. Induced pluripotent stem cells (iPSCs) have shown potential for cell transplantation treatment of neurodegenerative disorders. In the present study, the small molecules CHIR99021 and RepSox (CR) significantly facilitated reprogramming and enhanced the efficiency of GFP(+)/iPS-like colonies [rat iPSCs induced by OCT3/4, Sox2, Klf4, c-Myc, Nanog and Lin28 + CR (RiPSCs-6F/CR)] generation by similar to 4.0-fold during lentivirus-mediated reprogramming of six transcription factors in rat embryonic fibroblasts. The generation of iPSCs was detected by reverse transcription-PCR, immunofluorescence and western blot analysis. Subsequently, RiPSCs-6F/CR were stereotactically transplanted into the right medial forebrain bundle (MFB) of 6-hydroxydopamine-lesioned rats with PD. The transplanted RiPSCs-6F/CR survived and functioned in the MFB of rats with PD for >= 20 weeks, and significantly improved functional restoration from their PD-related behavioral defects. Furthermore, the grafted RiPSCs-6F/CR could migrate and differentiate into various neurocytes in vivo, including gamma aminobutyric acid-ergic, DA neurons and glial cells. In conclusion, the present study confirmed that RiPSCs-6F/CR induced by small molecules could be used as potential donor material for neural grafting to remodel basal ganglia circuitry in neurodegenerative diseases.

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