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Cell Res. 2012 Feb;22(2):321-32. doi: 10.1038/cr.2011.181. Epub 2011 Nov 22.

Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.

Author information

1
Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.

Abstract

Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of five transcriptional factors Mash1, Ngn2, Sox2, Nurr1, and Pitx3 can directly and effectively reprogram human fibroblasts into DA neuron-like cells. The reprogrammed cells stained positive for various markers for DA neurons. They also showed characteristic DA uptake and production properties. Moreover, they exhibited DA neuron-specific electrophysiological profiles. Finally, they provided symptomatic relief in a rat PD model. Therefore, our directly reprogrammed DA neuron-like cells are a promising source of cell-replacement therapy for PD.

PMID:
22105488
PMCID:
PMC3271588
DOI:
10.1038/cr.2011.181
[Indexed for MEDLINE]
Free PMC Article

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