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

Authors

  • Dali Yang,

    1. Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA
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  • Zhi-Jian Zhang,

    1. Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA
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  • Michael Oldenburg,

    1. Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA
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  • Melvin Ayala,

    1. Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA
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  • Su-Chun Zhang M.D., Ph.D.

    Corresponding author
    1. Departments of Anatomy and Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA
    • Waisman Center, Room T613, University of Wisconsin, 1500 Highland Avenue, Madison, Wisconsin 53705, USA. Telephone: 608-265-2543; Fax: 608-263-5267
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Abstract

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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