Glial cell line‐derived neurotrophic factor enhances in vitro differentiation of mid‐/hindbrain neural progenitor cells to dopaminergic‐like neurons

Parkinson's disease (PD) affects the motor system through the degeneration of the dopaminergic neurons of the substantia nigra. The use of human embryonic stem cell (hESC)‐derived human neural progenitor (hNP) cells provides a potential cell source for cell therapies and drug screens for future treatments. Glial cell line‐derived neurotrophic factor (GDNF) is a known dopaminergic neuroprotectant agent; however, its potential role in neural differentiation remains largely unknown. Addition of 25 ng/ml GDNF to hNP cell differentiation media, over a 21‐day period, induced a significantly (P < 0.05) greater portion of hNP cells to differentiate into dopaminergic neurons than non‐GDNF cultures, 50% compared with 2.9% of cells expressing tyrosine hydroxylase (TH), respectively. The hNP cells exposed to GDNF selectively expressed dopamine receptors 1, 4, and 5 and were evoked to release dopamine with KCl. This is the first report of GDNF and leukemia inhibitory factor enriching hESC‐derived hNP cells toward dopaminergic‐like neurons. © 2010 Wiley‐Liss, Inc.