Pluripotent stem cells for Parkinson's disease: progress and challenges.

Parkinson's disease (PD) is a common debilitating neurodegenerative disease. The motor symptoms of PD are caused mainly by a progressive loss of dopaminergic neurons from the substania nigra, resulting in a loss of dopamine production. Current therapies are palliative and, in the long term, ineffective. In addition, some can result in significant clinical side effects. The relatively localized pathology of PD makes it an ideal candidate for cell replacement therapy. Initial efforts focused on fetal cell transplantation, and significant clinical benefit lasting more than 10 years has been reported in some cases. However, the approach is controversial and results have been inconsistent. Inherent limitations of this approach for widespread use are the limited availability and variability of transplant material. In contrast, the self-renewal and differentiation potential of human pluripotent stem cells (hPSCs) make them a promising alternative cell source for cell replacement therapy for PD. Efforts in the past decade have demonstrated that hPSCs can be induced to differentiate in culture to functional dopaminergic neurons. Studies in delivering these cells into PD animal models have demonstrated survival, engraftment, and behavioral deficit improvements. Several groups are developing these cells with clinical trials in mind. Here, we review the state of the technology and consider the suitability of current manufacturing processes, cell purity, and tumorgenicity for clinical testing.