Abstract
Parkinson's disease (PD) is a neurodegenerative disease with the major pathology being the progressive loss of dopaminergic (DA) midbrain neurons in the substantia nigra. As early as in the 1980s, open-label clinical trials employing fetal ventral mesencephalon (fVM) tissues have demonstrated significant efficacy for PD treatment, which led to two NIH-sponsored double-blind placebo-controlled clinical trials. However, both trials showed only mild outcome. Retrospective analysis revealed several possible reasons that include patient selection, heterogeneity of grafts, immune recognition of grafts, lack of standardization of transplantation procedure and uneven distribution of grafts. Recent years have seen advances in reprogramming technologies which may provide solutions to the problems associated with fVM tissues. Induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) hold promise for generating clinical grade DA neural cells that are safe, homogeneous, scalable and standardizable. These new technologies may bring back clinical trials using cell therapy for PD treatment in the future.