Adult c-kitpos cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair

Georgina M. Ellison, Carla Vicinanza, Andrew J. Smith, Iolanda Aquila, Angelo Leone, Cheryl D. Waring, Beverley J. Henning, Giuliano Giuseppe Stirparo, Roberto Papait, Marzia Scarfò, Valter Agosti, Giuseppe Viglietto, Gianluigi Condorelli, Ciro Indolfi, Sergio Ottolenghi, Daniele Torella, Bernardo Nadal-Ginard

Research output: Contribution to journalArticle

Abstract

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-kit pos 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.

Original languageEnglish
Pages (from-to)827-842
Number of pages16
JournalCell
Volume154
Issue number4
DOIs
Publication statusPublished - Aug 15 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ellison, G. M., Vicinanza, C., Smith, A. J., Aquila, I., Leone, A., Waring, C. D., Henning, B. J., Stirparo, G. G., Papait, R., Scarfò, M., Agosti, V., Viglietto, G., Condorelli, G., Indolfi, C., Ottolenghi, S., Torella, D., & Nadal-Ginard, B. (2013). Adult c-kitpos cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell, 154(4), 827-842. https://doi.org/10.1016/j.cell.2013.07.039