Cell-Based Therapies for Parkinson's Disease: Past, Present, and Future

Parkinson's disease (PD) researchers have pioneered the use of cell-based therapies (CBTs) in the central nervous system. CBTs for PD were originally envisioned as a way to replace the dopaminergic nigral neurons lost with the disease. Several sources of catecholaminergic cells, including autografts of adrenal medulla and allografts or xenografts of mesencephalic fetal tissue, were successfully assessed in animal models, but their clinical translation has yielded poor results and much controversy. Recent breakthroughs on cell biology are helping to develop novel cell lines that could be used for regenerative medicine. Their future successful clinical application depends on identifying and solving the problems encountered in previous CBTs trials. In this review, we critically analyze past CBTs' clinical translation, the impact of the host in graft survival, and the role of preclinical studies and emerging new cell lines. We propose that the prediction of clinical results from preclinical studies requires experimental designs that allow blind data acquisition and statistical analysis, assessment of the therapy in models that parallel clinical conditions, looking for sources of complications or side effects, and limiting optimism bias when reporting outcomes. Antioxid. Redox Signal. 11, 2189-2208.