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PMID: 12077607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease.

Nature ·Vol. 418 ·No. 6893 ·2002-07-04 ·Pages 50-6

Kim JH, Auerbach JM, Rodríguez-Gómez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sánchez-Pernaute R, Bankiewicz K, McKay R

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.

MeSH Terms
Animals Blotting, Western Cell Differentiation Cell- and Tissue-Based Therapy/methods Chromatography, High Pressure Liquid DNA-Binding Proteins Disease Models, Animal Dopamine/metabolism Electrophysiology Embryo, Mammalian/cytology Female Mesencephalon/cytology,metabolism,pathology Neostriatum/cytology,metabolism Neurons/cytology,metabolism,pathology,transplantation Nuclear Receptor Subfamily 4, Group A, Member 2 Parkinson Disease/metabolism,pathology,therapy RNA, Messenger/genetics,metabolism Rats Rats, Sprague-Dawley Stem Cell Transplantation Stem Cells/cytology,metabolism Transcription Factors/genetics,metabolism Transfection
Chemicals
DNA-Binding Proteins Nr4a2 protein, mouse Nr4a2 protein, rat Nuclear Receptor Subfamily 4, Group A, Member 2 RNA, Messenger Transcription Factors Dopamine
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Kim Jong-Hoon
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Auerbach Jonathan M
Rodríguez-Gómez José A
Velasco Iván
Gavin Denise
Lumelsky Nadya
Lee Sang-Hun
Nguyen John
Sánchez-Pernaute Rosario
Bankiewicz Krys
McKay Ron
Article Info
Journal
Nature
Abbr.
Nature
ISSN
0028-0836
Published
2002-07-04
Epub
2002-00-20
Pages
50-6
Language
English
Region
England
NLM ID
0410462
Subset
IM
Corrections
CommentIn
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