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First published online October 18, 2007
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2007-0494v1
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Submitted on June 21, 2007
Accepted on October 9, 2007

EMBRYONIC STEM CELLS

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

Dali Yang 1, Zhi Jian Zhang 1, Michael Oldenburg 1, Melvin Ayala 1, Su Chun Zhang 1*

1 Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, WI 53705, USA.

* To whom correspondence should be addressed. E-mail: zhang{at}waisman.wisc.edu.


  Abstract

We show that human embryonic stem cell (hESC)-derived dopaminergic neurons survived transplantation to the neurotoxin 6-hydroxydopamine (6-OHDA) 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 to 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.

______________________________________________________________

D. Yang and Z-J Zhang contributed equally to this article.

 Key Words. Dopaminergic neurons, Cell therapy, Transplantation, Parkinson's disease, Rats




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