A Repair Tool-(c)Kit for the Injured Heart

Abstract

1. Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, et al. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell . 2013;154:827–842. 2. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324:98–102. 3. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–776. 4. Senyo SE, Steinhauser ML, Pizzimenti CL, Yang VK, Cai L, Wang M, et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2013;493:433–436. 5. Nelson TJ, Faustino RS, Chiriac A, Crespo-Diaz R, Behfar A, Terzic A. CXCR4+/FLK-1+ biomarkers select a cardiopoietic lineage from embryonic stem cells. Stem Cells. 2008;26:1464–1473. It is now accepted that the heart is a self-renewing organ,2 although its regenerative capacity is insufficient to restore healthy homeostasis after injury in human adults. Despite advances in characterization and attempts at modulating regeneration of the heart, the origin of newly formed cardiomyocytes is highly debated, with evidence independently supporting the existence of a critical stem cell compartment that supplies newly formed cardiomyocyte after injury3 or suggesting that division of mononucleated cardiomyocytes can replace lost cardiac cells.4 In this study, Ellison et al1 hypothesize that c-kit–positive endogenous cardiac stem cells (eCSCs) are the main source for new functional cardiomyocytes responsible for anatomic and functional recovery in the setting of acute heart failure caused by diffuse injury. Ellison et al1 applied a method of severe diffused myocardial damage caused by a single high dose of isoproterenol (ISO), originally described in adult rats, and translated it to a mouse model to allow lineage tracing experiments. The resulting injury was spontaneously reverted after 4 weeks, creating a system to study …