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Stem Cells International
Volume 2012, Article ID 412040, 17 pages
http://dx.doi.org/10.1155/2012/412040
Review Article

Cellular Programming and Reprogramming: Sculpting Cell Fate for the Production of Dopamine Neurons for Cell Therapy

1Laboratory of Stem Cells and Neural Repair, Fundacion Inbiomed, Paseo Mikeletegi 81, 20009 San Sebastian, Spain
2Department of Neuroscience, Karolinska Institutet, Retzius Road 8, 17177 Stockholm, Sweden

Received 18 March 2012; Accepted 5 July 2012

Academic Editor: Marcel M. Daadi

Copyright © 2012 Julio C. Aguila et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be applied in vitro to induce, select, and reprogram cells to the mesostriatal dopamine fate.