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

Abstract

Summary: 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). : Human ESCs are a potential source of regenerative medicine. However, safety and efficacy of ESC derivatives must be validated strictly before clinical application. Wang et al. manufactured clinical-grade human parthenogenetic ESC-derived DA neurons under CGMP conditions. The authors found that transplantation of these DA cells into monkeys was safe and provided preclinical data for human ESC-based clinical trials. Keywords: embryonic stem cell, Parkinson's disease, cell therapy, dopaminergic neuron, nonhuman primate, monkey