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EMBRYONIC STEM CELLS

Human Embryonic Stem Cell-Derived Dopaminergic Neurons Reverse Functional Deficit in Parkinsonian Rats

Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA

Key Words. Dopaminergic neurons • Cell therapy • Transplantation • Parkinson disease • Rats

Correspondence: Su-Chun Zhang, M.D., Ph.D., Waisman Center, Room T613, University of Wisconsin, 1500 Highland Avenue, Madison, Wisconsin 53705, USA. Telephone: 608-265-2543; Fax: 608-263-5267; e-mail: zhang{at}waisman.wisc.edu

Received June 21, 2007; accepted for publication October 9, 2007.
First published online in STEM CELLS EXPRESS   October 18, 2007.



We show that human embryonic stem cell-derived dopaminergic neurons survived transplantation to the neurotoxin 6-hydroxydopamine-lesioned rat striatum and, in combination with the cells newly differentiated from their progenitors, contributed to locomotive function recovery at 5 months. The animal behavioral improvement was correlated with the dopamine neurons present in the graft. Although the donor cells contained forebrain and midbrain dopamine neurons, the dopamine neurons present in the graft mainly exhibited a midbrain, or nigra, phenotype, suggesting the importance of midbrain dopamine neurons in functional repair. Furthermore, progenies of grafted cells were neurons and glia with greatly diminished mitotic activity by 5 months. Thus, the in vitro-produced human dopamine neurons can functionally engraft in the brain.

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

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