title: Matrix identity and tractional forces influence indirect cardiac reprogramming.
abstract: 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.
authors: Department of Biomedical Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan, 48109, USA.
authors: Yen P
authors: YP
authors: Kong
authors: Bita
authors: B
authors: Carrion
authors: Rahul K
authors: RK
authors: Singh
authors: Andrew J
authors: AJ
authors: Putnam
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D065150:Cellular Reprogramming; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix; D005337:Fibrin / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012038:Regeneration; D013917:Thrombin / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005337:Fibrin; D013917:Thrombin; D001205:Ascorbic Acid