Cell Biology

The Matter of the Heart

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Science  22 Jun 2012:
Vol. 336, Issue 6088, pp. 1483-1484
DOI: 10.1126/science.336.6088.1483-d
CREDIT: KSHITIZ ET AL., SCI. SIGNAL. 5, RA41 (2012)

Cell proliferation and differentiation are directed by specific transcription factors and signaling molecules, but recent studies show that matrix stiffness can also have a major effect. Kshitiz et al. used polyacrylamide gels with different rigidity values to show that substrate stiffness is important for the morphogenesis and differentiation of human and rat cardiosphere-derived progenitor cells (CDCs) toward the endothelial fate. The optimal rigidity matched that of heart tissue. When compared to cells cultured on glass, cells that had been cultured on a myocardium rigidity–mimicking substratum (MRS) showed better survival and better integration into blood vessels, and expressed factors associated with endothelial differentiation when applied to a rat model of myocardial infarction. A c-Kit–positive cell population was implicated as the source of CDC-derived endothelium, with p190RhoGAP involved in this process via RhoA-dependent and independent mechanisms. Down-regulation of p190RhoGAP was sufficient to bias cell differentiation toward the endothelial lineage, whereas its up-regulation favored the cardiomyogenic lineage. Thus, the rigidity of the cell environment in cardiac tissue affects cell proliferation and differentiation, which could be important when considering thera peutic interventions.

Sci. Signal. 5, ra41 (2012).

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