Therapeutic Potential of PSC-derived Cell Transplantation in Parkinson's Disease: A Systematic Review and Meta-analysis of Preclinical Studies

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disease with debilitating clinical presentations. Common therapeutic approaches for symptomatic improvement are often effective for a temporary period of time, after which patients often experience progressive disabilities. Cell replacement therapy is a potential therapeutic method that aims to replace depleted mesencephalic dopaminergic (DA) neurons, which may control symptoms and halt disease progression. Preclinical studies have investigated the efficacy of these PSC-derived DA cells in animal models of PD. METHODS: In this study, we comprehensively examine preclinical data on the therapeutic effect of primate PSC-derived DA progenitors on motor deficits in animal models of PD as a precursor for conducting human clinical trials. Relevant articles published before August 14th, 2023, were obtained from PubMed, Scopus, and Web of Science. RESULTS: Through several rounds of screening, 46 studies that met our inclusion criteria were included in this study. The quality of each study was assessed using CAMARADES and SYRCLE approaches. Although no included studies were judged to have an overall high risk of bias, several studies exhibited domain-specific methodological limitations. The analyzed studies demonstrate that cell therapy significantly improves motor dysfunction in rodent and non-human primate models of PD. CONCLUSION: This systematic review and meta-analysis demonstrate that PSC-based cell therapy significantly improves motor dysfunction in rodent and NHP models of PD and could be a promising approach for halting disease progression, improving behavioral manifestations of the disease, and increasing the overall quality of life in PD.