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.
Young
Amber
A
Biomedical and Health Science Institute, Athens, Georgia, USA.
Assey
Kristin S
KS
Sturkie
Carla D
CD
West
Franklin D
FD
Machacek
David W
DW
Stice
Steven L
SL
D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002469:Cell Separation; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016133:Polymerase Chain Reaction
D051100:Glial Cell Line-Derived Neurotrophic Factor; D004298:Dopamine