Feng Su, Zhang Ting, Ke Wei, Xiao Yujie, Guo Zhong, Lu Chunling, Li Shuntang, Guo Zhongxin, Liu Yuanyuan, Tan Guohe, Chen Yingying, Yue Feng, Shu Yousheng, Yue Chunmei, Jing Naihe
Bioland Laboratory/Guangzhou Laboratory, Guangzhou 510005, China.
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai 200031, China.
Life Med. 2022 Jun 28;1(2):196-206. doi: 10.1093/lifemedi/lnac008. eCollection 2022 Oct.
Human induced neural stem/progenitor cells (iNPCs) are a promising source of cells for stem cell-based therapy. The therapeutic potential of human iNPCs has been extensively tested in animal models, including both mouse and monkey models. However, the comprehensive characterization of grafted iNPCs in the brain of non-human primates has been lagged behind. In this study, we transplanted human iNPCs into the basal forebrain of adult cynomolgus monkeys. We found that grafted iNPCs predominantly differentiated into neurons that displayed long-term survival up to 12 months. Additionally, iNPC-derived human neurons gradually matured in term of morphology and subtype differentiation. More excitingly, we observed that human neurons displayed electrophysiological activities resembling those of mature neurons, indicating the acquisition of functional membrane properties. Collectively, this study systematically characterized human iNPCs in the brain of non-human primates, and will provide invaluable clues for developing safe and effective stem cell-based therapies for different brain disorders.
人诱导神经干细胞/祖细胞（iNPCs）是基于干细胞治疗的一种很有前景的细胞来源。人iNPCs的治疗潜力已在动物模型中进行了广泛测试，包括小鼠和猴子模型。然而，在非人灵长类动物大脑中移植的iNPCs的全面表征一直滞后。在本研究中，我们将人iNPCs移植到成年食蟹猴的基底前脑。我们发现移植的iNPCs主要分化为神经元，这些神经元可长期存活长达12个月。此外，iNPC衍生的人类神经元在形态和亚型分化方面逐渐成熟。更令人兴奋的是，我们观察到人类神经元表现出类似于成熟神经元的电生理活动，表明其获得了功能性膜特性。总体而言，本研究系统地表征了非人灵长类动物大脑中的人iNPCs，并将为开发针对不同脑部疾病的安全有效的基于干细胞的疗法提供宝贵线索。
