Research ArticleStem Cells

Matrix Rigidity Controls Endothelial Differentiation and Morphogenesis of Cardiac Precursors

Sci. Signal.  05 Jun 2012:
Vol. 5, Issue 227, pp. ra41
DOI: 10.1126/scisignal.2003002

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The Heart of the Matrix

Cardiosphere-derived cells (CDCs) are adult stem cells with the potential to differentiate into endothelial cells and cardiomyocytes, which are the major cell types of the heart. Their potential to induce cardiac regeneration after myocardial infarct is currently being clinically tested. Kshitiz et al. showed that CDCs cultured on a substrate with a rigidity matching that of normal myocardium yielded higher proportions of cells with the adhesion molecule CD31 (a marker of differentiated endothelial cells) than did those cultured on less or more rigid substrata. CDCs cultured on substratum equivalent in rigidity to the myocardium developed into organized cellular networks reminiscent of blood vessels and appeared to integrate more efficiently into the vasculature of ischemic rat myocardium. The process of sensing substratum rigidity occurred throughout the in vitro culture period, and the signaling pathway involved required the guanosine triphosphatase (GTPase)–activating protein p190RhoGAP acting through various downstream effectors, including the GTPase RhoA. These results could potentially increase the efficacy of regenerative therapies that use CDCs to repair hearts after myocardial infarction.