Following intensive efforts since their discovery little more than 10 years ago, cell replacement therapy using induced pluripotent stem (iPS) cells is now becoming reality. However, there remain several obstacles in the translation of basic research to clinical application, obstacles known as the “Valley of Death”. With regards to regenerative medicine using iPS cells for Parkinson's disease, we have developed a method for the 1) efficient induction of dopaminergic neurons from human iPS cells and 2) sorting dopaminergic progenitor cells using a floor plate marker, CORIN. The grafted CORIN⁺ cells survived well and functioned as midbrain dopaminergic neurons in the Parkinson's disease model rats and monkeys, and showed minimal risk of tumor formation. Based on these results, we performed a pre-clinical study using a clinical-grade iPS cell line and finally started a clinical trial to treat Parkinson's disease patients in August 2018. Here, I discuss the key issues to crossing the Valley of Death: scientific rationale, pre-clinical study, and clinical trial.

自大约10年前被发现以来，经过大量努力，使用诱导性多能干（iPS）细胞进行细胞替代治疗现已成为现实。然而，将基础研究转化为临床应用仍然存在一些障碍，这些障碍被称为“死亡之谷”。关于使用iPS细胞治疗帕金森氏病的再生医学，我们已经开发出一种方法：1）从人iPS细胞有效诱导多巴胺能神经元，以及2）使用底板标记物CORIN筛选多巴胺能祖细胞。接枝CORIN ⁺细胞在帕金森氏病模型大鼠和猴子中存活良好，并起中脑多巴胺能神经元的作用，并显示出最小的肿瘤形成风险。基于这些结果，我们使用临床级iPS细胞系进行了临床前研究，并最终于2018年8月开始了治疗帕金森氏病患者的临床试验。在这里，我讨论穿越死亡之谷的关键问题：科学基本原理，临床前研究和临床试验。