Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells

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.

Generation of Dopamine Neurons from Rodent Fibroblasts through the Expandable Neural Precursor Cell Stage

“…Similar to our study, previous studies addressed the in vivo functionality of DA neurons directly converted from fibroblasts in transplanted PD rats (34,35). Among these studies, the behavioral recovery and DA neuron yield in the study by Kim et al are comparable with our findings.…”

The 2013 special issue on stem cell biology

“…Along the way, the field of stem cell biology has naturally become an important research area covered by papers published in Cell Research [2]. For instance, in the past year of 2012, Cell Research has published a number of important papers related to the stem cell field, covering diverse aspects and topics such as induced pluripotent stem (iPS) cells [3][4][5][6][7], mechanistic studies of pluripotency and differentiation [8][9][10][11], modeling of human diseases using stem cell-based systems [6,12], direct reprogramming of somatic cells to other cell types without passing through an pluripotent intermediate [13][14][15][16], as well as neural crest stem cells [17] and cancer stem cells [18][19][20].…”

Vers une régénération induite du système nerveux

“…La transplantation de neurones obtenus in vitro n'est en effet pas synonyme de survie, d'inté-gration et de restauration des fonctions neuronales perdues, surtout lorsqu'elle est envisagée dans le contexte extracellulaire du cerveau adulte pathologique. Si cette stratégie s'est avérée bénéfique dans un modèle murin de maladie de Parkinson [21,22], l'approche chirurgicale apparaît plus délicate à mettre en oeuvre chez l'homme. Dans le cas de la maladie de Parkinson, la transplantation de tissu mésencéphalique ventral (enrichi en progéniteurs dopaminergiques), provenant de foetus humains, a produit des résultats mitigés mais néanmoins prometteurs [23].…”