Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease
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 abilit...
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| Veröffentlicht in: | Nature (London) 2002-07, Vol.418 (6893), p.50-56 |
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| creator | McKay, Ron Kim, Jong-Hoon Auerbach, Jonathan M Rodríguez-Gómez, José A Velasco, Iván Gavin, Denise Lumelsky, Nadya Lee, Sang-Hun Nguyen, John Sánchez-Pernaute, Rosario Bankiewicz, Krys |
| description | 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. |
| doi_str_mv | 10.1038/nature00900 |
| format | Article |
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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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature00900</identifier><identifier>PMID: 12077607</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Animal diseases ; Animal models ; Animals ; Blotting, Western ; Brain ; Cell Differentiation ; Cell- and Tissue-Based Therapy - methods ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; DNA-Binding Proteins ; Dopamine - metabolism ; Electrophysiology ; Embryo, Mammalian - cytology ; Embryos ; Female ; Mesencephalon - cytology ; Mesencephalon - metabolism ; Mesencephalon - pathology ; Neostriatum - cytology ; Neostriatum - metabolism ; Neurons ; Neurons - cytology ; Neurons - metabolism ; Neurons - pathology ; Neurons - transplantation ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; Parkinson Disease - metabolism ; Parkinson Disease - pathology ; Parkinson Disease - therapy ; Parkinson's disease ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Stem Cell Transplantation ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transfection</subject><ispartof>Nature (London), 2002-07, Vol.418 (6893), p.50-56</ispartof><rights>COPYRIGHT 2002 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Jul 4, 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-70c27ddce3a42080753ac7aa1633afb154f841954e2b271c5279ee194a8f74b83</citedby><cites>FETCH-LOGICAL-c539t-70c27ddce3a42080753ac7aa1633afb154f841954e2b271c5279ee194a8f74b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12077607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McKay, Ron</creatorcontrib><creatorcontrib>Kim, Jong-Hoon</creatorcontrib><creatorcontrib>Auerbach, Jonathan M</creatorcontrib><creatorcontrib>Rodríguez-Gómez, José A</creatorcontrib><creatorcontrib>Velasco, Iván</creatorcontrib><creatorcontrib>Gavin, Denise</creatorcontrib><creatorcontrib>Lumelsky, Nadya</creatorcontrib><creatorcontrib>Lee, Sang-Hun</creatorcontrib><creatorcontrib>Nguyen, John</creatorcontrib><creatorcontrib>Sánchez-Pernaute, Rosario</creatorcontrib><creatorcontrib>Bankiewicz, Krys</creatorcontrib><title>Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease</title><title>Nature (London)</title><addtitle>Nature</addtitle><description>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.</description><subject>Animal diseases</subject><subject>Animal models</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Brain</subject><subject>Cell Differentiation</subject><subject>Cell- and Tissue-Based Therapy - methods</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Disease Models, Animal</subject><subject>DNA-Binding Proteins</subject><subject>Dopamine - metabolism</subject><subject>Electrophysiology</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryos</subject><subject>Female</subject><subject>Mesencephalon - cytology</subject><subject>Mesencephalon - metabolism</subject><subject>Mesencephalon - pathology</subject><subject>Neostriatum - cytology</subject><subject>Neostriatum - metabolism</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - 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neurons derived from embryonic stem cells function in an animal model of Parkinson's disease</title><author>McKay, Ron ; Kim, Jong-Hoon ; Auerbach, Jonathan M ; Rodríguez-Gómez, José A ; Velasco, Iván ; Gavin, Denise ; Lumelsky, Nadya ; Lee, Sang-Hun ; Nguyen, John ; Sánchez-Pernaute, Rosario ; Bankiewicz, Krys</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-70c27ddce3a42080753ac7aa1633afb154f841954e2b271c5279ee194a8f74b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animal diseases</topic><topic>Animal models</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Brain</topic><topic>Cell Differentiation</topic><topic>Cell- and Tissue-Based Therapy - methods</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Disease Models, Animal</topic><topic>DNA-Binding Proteins</topic><topic>Dopamine - metabolism</topic><topic>Electrophysiology</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryos</topic><topic>Female</topic><topic>Mesencephalon - cytology</topic><topic>Mesencephalon - metabolism</topic><topic>Mesencephalon - pathology</topic><topic>Neostriatum - cytology</topic><topic>Neostriatum - metabolism</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neurons - transplantation</topic><topic>Nuclear Receptor Subfamily 4, Group A, Member 2</topic><topic>Parkinson Disease - metabolism</topic><topic>Parkinson Disease - pathology</topic><topic>Parkinson Disease - therapy</topic><topic>Parkinson's disease</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Stem Cell Transplantation</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - 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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. 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| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2002-07, Vol.418 (6893), p.50-56 |
| issn | 0028-0836 1476-4687 |
| language | eng |
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| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | Animal diseases Animal models Animals Blotting, Western Brain Cell Differentiation Cell- and Tissue-Based Therapy - methods Chromatography, High Pressure Liquid Disease Models, Animal DNA-Binding Proteins Dopamine - metabolism Electrophysiology Embryo, Mammalian - cytology Embryos Female Mesencephalon - cytology Mesencephalon - metabolism Mesencephalon - pathology Neostriatum - cytology Neostriatum - metabolism Neurons Neurons - cytology Neurons - metabolism Neurons - pathology Neurons - transplantation Nuclear Receptor Subfamily 4, Group A, Member 2 Parkinson Disease - metabolism Parkinson Disease - pathology Parkinson Disease - therapy Parkinson's disease Rats Rats, Sprague-Dawley RNA, Messenger - genetics RNA, Messenger - metabolism Stem Cell Transplantation Stem cells Stem Cells - cytology Stem Cells - metabolism Transcription Factors - genetics Transcription Factors - metabolism Transfection |
| title | Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease |
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