4.8 Article

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Journal

BIOMATERIALS
Volume 85, Issue -, Pages 180-194

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.01.066

Keywords

Direct transdifferentiation; Direct reprogramming; Smooth muscle cell differentiation; Myocardin; Tissue-engineered blood vessel

Funding

  1. NIH [UH2TR000505, 4UH3TR000505]
  2. NIH Common Fund for the Micro physiological Systems Initiative

Ask authors/readers for more resources

Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYHM, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction. (C) 2016 Elsevier Ltd. All rights reserved.

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