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

Naturevolume 418pages5056 (2002) | Download Citation

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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.

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Acknowledgements

We thank J. Harvey-White for technical assistance with HPLC, P. Brasted for advice on the non-pharmacological evaluation of the grafted animals, and J. Kordower for supplying boxes for the paw-reaching test, E. Lai for the anti-bB1 antibody and G. Corte for the anti-OTX2 antibody. We thank D. Owens for critical discussion of the manuscript. J.A.R.-G. was supported by a postdoctoral fellowship from the Spanish Ministerio de Educación, Cultura y Deporte. I.V. is a Pew Latin American fellow. We thank the National Parkinson Foundation and the Tuchman Foundation for their support.

Author information

Author notes

    • Jonathan M. Auerbach

    Present address: NeuralStem, Inc., 205 Perry Parkway, Gaithersburg, Maryland, 20877, USA

    • Sang-Hun Lee

    Present address: Department of Biochemistry, College of Medicine, Hanyang University, 133-791, Seoul, Korea

    • John Nguyen
    •  & Krys Bankiewicz

    Present address: Department of Neurosurgery, University of California, San Francisco, California, 94103, USA

    • Rosario Sánchez-Pernaute

    Present address: Neuroregeneration Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, 02478, USA

  1. Jong-Hoon Kim, Jonathan M. Auerbach, Sang-Hun Lee, John Nguyen, Rosario Sánchez-Pernaute and Krys Bankiewicz: These authors contributed equally to this work.

  2. Ron McKay: Correspondence and requests for materials should be addressed to R.M.

Affiliations

  1. Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, Maryland, 20892, USA

    • Jong-Hoon Kim
    • , José A. Rodríguez-Gómez
    • , Iván Velasco
    • , Denise Gavin
    • , Nadya Lumelsky
    • , Sang-Hun Lee
    • , John Nguyen
    • , Rosario Sánchez-Pernaute
    • , Krys Bankiewicz
    •  & Ron McKay

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Competing interests

The authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Ron McKay.

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https://doi.org/10.1038/nature00900

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