title: Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease.
abstract: Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Auerbach
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez-Gómez
authors.forename: Iván
authors.initials: I
authors.lastname: Velasco
authors.forename: Denise
authors.initials: D
authors.lastname: Gavin
authors.forename: Nadya
authors.initials: N
authors.lastname: Lumelsky
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: Nguyen
authors.forename: Rosario
authors.initials: R
authors.lastname: Sánchez-Pernaute
authors.forename: Krys
authors.initials: K
authors.lastname: Bankiewicz
authors.forename: Ron
authors.initials: R
authors.lastname: McKay
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C539883:Nr4a2 protein, mouse; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D014157:Transcription Factors; D004298:Dopamine