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EMBRYONIC STEM CELLS

Persistent Dopamine Functions of Neurons Derived from Embryonic Stem Cells in a Rodent Model of Parkinson Disease

^aLaboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Porter Neuroscience Research Center;
^bMolecular Imaging Branch, National Institute of Mental Health; and
^cClinical Center, National Institutes of Health, Bethesda, Maryland, USA;
^dMedical Department, Brookhaven National Laboratory, Upton, New York, USA;
^eLaboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA

Key Words. Parkinson disease • Embryonic stem cell • Transplantation • Microdialysis • Positron emission tomography Dopamine transporter

Correspondence: Ron D.G. McKay, Ph.D., Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, 35 Convent Drive, Building 35, Room 3A-201, MSC 3703, Bethesda, Maryland 20892, USA. Telephone: 301-496-6574; Fax: 301-402-4738; e-mail: mckayr{at}ninds.nih.gov

Received June 26, 2006; accepted for publication December 5, 2006.
First published online in STEM CELLS EXPRESS   December 14, 2006.



The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D₂ receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.

Disclosure of potential conflicts of interest is found at the end of this article.

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