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Embryonic Stem Cells |
1 Laboratory of Molecular Biology, NINDS Porter Neuroscience Research Center, National Institutes of Health, Bethesda, Maryland
2 Molecular Imaging Branch, NIMH, National Institutes of Health, Bethesda, Maryland
3 Medical Department, Brookhaven National Laboratory, Upton, New York
4 Clinical Center, National Institutes of Health, Bethesda, Maryland
5 Medical Department, Brookhaven National Laboratory, Upton, New York; Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
* To whom correspondence should be addressed. E-mail: mckayr{at}ninds.nih.gov.
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Abstract |
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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 DA release was induced by depolarization and pharmacological stimulants. Positron emission tomography (PET) measured the expression of pre-synaptic dopamine transporters (DAT) 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, reuptake and stimulate appropriate post-synaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.
Key Words. Parkinson's disease, embryonic stem cell, transplantation, microdialysis, positron emission tomography, dopamine transporter
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