Matrix identity and tractional forces influence indirect cardiac reprogramming

Sci Rep. 2013 Dec 11;3:3474. doi: 10.1038/srep03474.


Heart regeneration through in vivo cardiac reprogramming has been demonstrated as a possible regenerative strategy. While it has been reported that cardiac reprogramming in vivo is more efficient than in vitro, the influence of the extracellular microenvironment on cardiac reprogramming remains incompletely understood. This understanding is necessary to improve the efficiency of cardiac reprogramming in order to implement this strategy successfully. Here we have identified matrix identity and cell-generated tractional forces as key determinants of the dedifferentiation and differentiation stages during reprogramming. Cell proliferation, matrix mechanics, and matrix microstructure are also important, but play lesser roles. Our results suggest that the extracellular microenvironment can be optimized to enhance cardiac reprogramming.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Cell Dedifferentiation
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation / drug effects
  • Cellular Reprogramming*
  • Collagen Type I / metabolism
  • Extracellular Matrix
  • Fibrin / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Mice
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Regeneration*
  • Thrombin / pharmacology


  • Collagen Type I
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Fibrin
  • Thrombin
  • Ascorbic Acid