title: Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair.
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-kit(pos) eCSCs are necessary and sufficient for the regeneration and repair of myocardial damage.
authors: Stem Cell and Regenerative Biology Unit (BioStem), Liverpool John Moores University, Liverpool L3 3AF, UK.
authors: Georgina M
authors: GM
authors: Ellison
authors: Carla
authors: C
authors: Vicinanza
authors: Andrew J
authors: AJ
authors: Smith
authors: Iolanda
authors: I
authors: Aquila
authors: Angelo
authors: A
authors: Leone
authors: Cheryl D
authors: CD
authors: Waring
authors: Beverley J
authors: BJ
authors: Henning
authors: Giuliano Giuseppe
authors: GG
authors: Stirparo
authors: Roberto
authors: R
authors: Papait
authors: Marzia
authors: M
authors: Scarfò
authors: Valter
authors: V
authors: Agosti
authors: Giuseppe
authors: G
authors: Viglietto
authors: Gianluigi
authors: G
authors: Condorelli
authors: Ciro
authors: C
authors: Indolfi
authors: Sergio
authors: S
authors: Ottolenghi
authors: Daniele
authors: D
authors: Torella
authors: Bernardo
authors: B
authors: Nadal-Ginard
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis; D006321:Heart / Q000502:physiology; D006333:Heart Failure / Q000139:chemically induced / Q000628:therapy*; D006801:Humans; D007545:Isoproterenol; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D019089:Stem Cell Factor / Q000378:metabolism
chemical_list: D019089:Stem Cell Factor; D049452:Green Fluorescent Proteins; D007545:Isoproterenol