A simple, rapid, efficient, and specialized culture system was successfully developed in this study to induce human embryonic stem cells into dopaminergic neurons in vitro. It only took 5 days to generate quickly and directly a large number of homogeneous neural stem cell (NSC) spheres by the introduction of small molecules LDN (inhibitor of BMP [bone morphogenetic protein] pathway that inhibits BMP type I receptors ALK2 and ALK3), SB431542 (inhibitor of TGF-β/Activin/Dodal pathway that inhibits ALK4, ALK5, and ALK7), CHIR99021 (inhibitors of GSK-3 [glycogen synthase kinase 3]), and basic fibroblast growth factor (bFGF). The dopaminergic neurons were successfully induced at day 25 (tyrosine hydroxylase [TH] expressed) and at day 32 (TH highly expressed) with high purity (TH/Tuj1: 84.14% and 93.15%, respectively) by the addition of FGF8 (fibroblast growth factor 8), sonic hedgehog (SHH), and Purmorphamine after the generation of NSC at day 5. And, the dopaminergic neurons induced by this system successfully survived and integrated into the striatum of cynomolgus monkey brain after transplantation, which verified the efficiency of the induction system developed in this study, suggesting the potential clinical application in cell therapy for neurological diseases.

中文翻译：

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人胚胎干细胞体外诱导入中脑多巴胺能神经元并在食蟹猴中移植。

在这项研究中成功开发了一种简单，快速，高效且专门的培养系统，以诱导人胚胎干细胞体外产生多巴胺能神经元。通过引入小分子LDN（抑制BMP I型受体ALK2和ALK3的BMP [骨形态发生蛋白]抑制剂），仅需5天即可快速，直接生成大量同质神经干细胞（NSC）球， SB431542（抑制ALK4，ALK5和ALK7的TGF-β/ Activin / Dodal途径抑制剂），CHIR99021（GSK-3 [糖原合酶激酶3]抑制剂）和碱性成纤维细胞生长因子（bFGF）。多巴胺能神经元在第25天（酪氨酸羟化酶[TH]表达）和第32天（TH高表达）成功诱导出高纯度（TH / Tuj1：84.14％和93.15％），