Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair

• Published in: Cell 2013-08, Vol.154 (4), p.827-842
• Main Authors: Ellison, Georgina M., Vicinanza, Carla, Smith, Andrew J., Aquila, Iolanda, Leone, Angelo, Waring, Cheryl D., Henning, Beverley J., Stirparo, Giuliano Giuseppe, Papait, Roberto, Scarfò, Marzia, Agosti, Valter, Viglietto, Giuseppe, Condorelli, Gianluigi, Indolfi, Ciro, Ottolenghi, Sergio, Torella, Daniele, Nadal-Ginard, Bernardo
• Format: Article
• Language: English
• Subjects: adults; animal models; cardiac output; cardiomyocytes; heart failure; progeny; stem cells
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2013.07.039

The epidemic of heart failure has stimulated interest in understanding cardiac regeneration. Evidence has been reported supporting regeneration via transplantation of multiple cell types, as well as replication of postmitotic cardiomyocytes. In addition, the adult myocardium harbors endogenous c-kitpos cardiac stem cells (eCSCs), whose relevance for regeneration is controversial. Here, using different rodent models of diffuse myocardial damage causing acute heart failure, we show that eCSCs restore cardiac function by regenerating lost cardiomyocytes. Ablation of the eCSC abolishes regeneration and functional recovery. The regenerative process is completely restored by replacing the ablated eCSCs with the progeny of one eCSC. eCSCs recovered from the host and recloned retain their regenerative potential in vivo and in vitro. After regeneration, selective suicide of these exogenous CSCs and their progeny abolishes regeneration, severely impairing ventricular performance. These data show that c-kitpos eCSCs are necessary and sufficient for the regeneration and repair of myocardial damage. [Display omitted] •The adult myocardium contains stem cells with intrinsic regenerative capacity•These c-kitpos eCSCs are necessary and sufficient for myocardial regeneration•Ablation of eCSCs and their progeny abolishes regeneration and functional recovery•In-vitro-grown CSCs home to the damaged myocardium and can replace the ablated cohort Multiple approaches and injury models provide evidence for the necessity and sufficiency of c-kit-positive cardiac stem cells to functionally repair and regenerate injured heart tissue in adult rodents.