Isolation, characterization and ex vivo amplification of heart-derived c-kit progenitor cells for cellular therapy

The myocardium contains a resident progenitor cells, named cardiac progenitor cells, that maintain the heart homeostasis by replacing lost myocytes. The c-kit tyrosine kinase receptor is one of the principal markers defining cardiac progenitors in the adult mammalian heart, including human. C-kit+ cardiac progenitors have been recently identified as a multipotent cells population able to give rise to myocardial, endothelial and smooth muscle both in vitro and in vivo. The discovery of cardiac progenitors and the devise of culture systems to amplify these cells in culture without loosing their differentiation potency has opened new perspectives for clinical applications aimed at replacing myocardium lost as a consequence of acute or chronic ischemic disease. While cardiac progenitors have been deeply investigated for their stem cell activity, susceptibility to stress conditions and aging, and their ability to repair the infarcted heart, their origin, phenotype and biological features have been disclosed only in part. In the present study, we report that c-kit+ cardiac progenitors derived from the human heart express markers in common with mesenchymal stem cells. Our in vitro analyses revealed that, compared to bone marrow-derived mesenchymal cells, c-kit+ cardiac progenitors have a reduced ability to differentiate into canonical mesenchymal cellular derivatives such as osteoblasts and adipocytes; by contrast, under appropriate differentiation conditions, these cells gave rise to tubular-like structures at the same extent as endothelial cells, expressed smooth muscle cells markers, and expressed early and late myocardial markers. These findings suggest that ex-vivo amplified c-kit+ cardiac progenitors differentiate into mesenchymal cells having a preferentially myocardial commitment.