State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Stem Cell Bank, Chinese Academy of Sciences, Beijing 100190, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Stem Cell Reports. 2018 Jul 10;11(1):171-182. doi: 10.1016/j.stemcr.2018.05.010. Epub 2018 Jun 14.
Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD (ClinicalTrials.gov number NCT03119636).
临床应用干细胞衍生物需要临床级别的细胞，并充分预先证明安全性和有效性，最好在灵长类动物中进行。我们之前成功建立了临床级别的人孤雌胚胎干细胞（hPESC）系，但其亚型特异性后代用于治疗的适用性尚不清楚。在这里，我们在灵长类帕金森病（PD）模型的两种规范方案中比较了临床级 hPESC 衍生的中脑多巴胺能（DA）神经元的功能。我们发现，移植物没有形成肿瘤，并在两组大多数猴子中至少 24 个月产生了不同但明显的行为改善。此外，纹状体中的微量 DA 增加与显著的功能改善相关。这些结果表明，临床级 hPESCs 可以作为 PD 治疗的可靠细胞来源。我们的概念验证结果为中国首个基于 ESC 的 PD 临床研究的 I/IIa 期临床试验（ClinicalTrials.gov 编号：NCT03119636）提供了临床前数据。
