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

• Published in: Stem cells (Dayton, Ohio) Vol. 25; no. 4; pp. 918 - 928
• Main Authors: Rodríguez‐Gómez, Jose A., Lu, Jian‐Qiang, Velasco, Iván, Rivera, Seth, Zoghbi, Sami S., Liow, Jeih‐San, Musachio, John L., Chin, Frederick T., Toyama, Hiroshi, Seidel, Jurgen, Green, Michael V., Thanos, Panayotis K., Ichise, Masanori, Pike, Victor W., Innis, Robert B., McKay, Ron D. G.
• Format: Journal Article
• Language: English
• Published: Bristol John Wiley & Sons, Ltd 01.04.2007
• Subjects: Animals; Cell Differentiation; Disease Models, Animal; Dopamine - physiology; Embryonic stem cell; Embryonic Stem Cells - pathology; Embryonic Stem Cells - physiology; Female; Hydroxydopamines - pharmacology; Immunohistochemistry; Mice; Microdialysis; Neurons - cytology; Neurons - physiology; Parkinson disease; Parkinsonian Disorders - pathology; Parkinsonian Disorders - physiopathology; Positron emission tomography Dopamine transporter; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation; Stereotyped Behavior; Transplantation
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1634/stemcells.2006-0386

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.