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Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons

Cited 65 time in Web of Science Cited 71 time in Scopus
Authors

Yoo, Junsang; Noh, Myungkyung; Kim, Hongnam; Jeon, Noo Li; Kim, Byung-Soo; Kim, Jongpil

Issue Date
2015-03
Publisher
Pergamon Press Ltd.
Citation
Biomaterials, Vol.45, pp.36-45
Abstract
The generation of dopaminergic (DA) neurons via direct lineage reprogramming can potentially provide a novel therapeutic platform for the study and treatment of Parkinson's disease. Here, we showed that nanoscale biophysical stimulation can promote the direct lineage reprogramming of somatic fibroblasts to induced DA (iDA) neurons. Fibroblasts that were cultured on flat, microgrooved, and nanogrooved substrates responded differently to the patterned substrates in terms of cell alignment. Subsequently, the DA marker expressions, acquisition of mature DA neuronal phenotypes, and the conversion efficiency were enhanced mostly on the nanogrooved substrate. These results may be attributed to specific histone modifications and transcriptional changes associated with mesenchymal-to-epithelial transition. Taken together, these results suggest that the nanopatterned substrate can serve as an efficient stimulant for direct lineage reprogramming to iDA neurons, and its effectiveness confirms that substrate nanotopography plays a critical role in the cell fate changes during direct lineage reprogramming. (C) 2014 Elsevier Ltd. All rights reserved.
ISSN
0142-9612
URI
https://hdl.handle.net/10371/204286
DOI
https://doi.org/10.1016/j.biomaterials.2014.12.049
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  • College of Engineering
  • School of Chemical and Biological Engineering
Research Area biomaterials, nanomedicine, regenerative medicine

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