C-kit+ cardiac progenitors exhibit mesenchymal markers and preferential cardiovascular commitment.

AIMS The heart contains c-kit(+) progenitors that maintain cardiac homeostasis. Cardiac c-kit(+) cells are multipotent and give rise to myocardial, endothelial and smooth muscle cells, both in vitro and in vivo. C-kit(+) cells have been thoroughly investigated for their stem cell activity, susceptibility to stress conditions and ageing, as well as for their ability to repair the infarcted heart. Recently, expression of mesenchymal stem cell (MSC) markers and MSC differentiation potency have been reported in cardiac progenitor cells. Based on this evidence, we hypothesized that c-kit(+) cells may have phenotypic and functional features in common with cardiac MSCs. METHODS AND RESULTS Culture of cells obtained from enzymatic dissociation of heart auricle fragments produced a fast-growing fibroblast-like population expressing mesenchymal markers. C-kit(+) cells co-expressing MSC markers were identified in this population, sorted by flow cytometry and cultured in the presence or the absence of unselected cardiac cells from the same patients. Subsets of c-kit(+) cells also co-expressed MSCs markers in vivo, as detected by immunofluorescence analysis of auricle tissue. Ex vivo expanded c-kit(+) cells produced osteoblasts and adipocytes, although less preferentially than bone marrow-derived MSCs, possessed vascular smooth muscle cell features and were induced to differentiate into endothelium-like and cardiac-like cells. CONCLUSION In line with previous findings, our results indicate that c-kit(+) cardiac progenitors are primitive stem cells endowed with multilineage differentiation ability. They further suggest a possible relationship between these cells and a heart-specific MSC population with cardiovascular commitment potential.