Human Clinical-Grade Parthenogenetic ESC-Derived Dopaminergic Neurons?Recover Locomotive Defects of Nonhuman Primate Models of?Parkinson's Disease

摘要

Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably inprimates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but thesuitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derivedmidbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson’s disease (PD) model. We found that the graftsdid not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in bothgroups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstratedthat clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical datafor China’s first ESC-based phase I/IIa clinical study of PD (ClinicalTrials.gov number NCT03119636).