title: Glial cell line-derived neurotrophic factor enhances in vitro differentiation of mid-/hindbrain neural progenitor cells to dopaminergic-like neurons.
abstract: 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.
authors.affiliation: Biomedical and Health Science Institute, Athens, Georgia, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Young
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Assey
authors.forename: Carla D
authors.initials: CD
authors.lastname: Sturkie
authors.forename: Franklin D
authors.initials: FD
authors.lastname: West
authors.forename: David W
authors.initials: DW
authors.lastname: Machacek
authors.forename: Steven L
authors.initials: SL
authors.lastname: Stice
mesh_terms: 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
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D004298:Dopamine