Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair
Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair
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DOI：
10.1016/j.cell.2013.07.039
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发表时间：
2013-08-15
期刊：
影响因子：
64.5
通讯作者：
Nadal-Ginard, Bernardo
中科院分区：
文献类型：
--
作者：
Ellison, Georgina M.;Vicinanza, Carla;Nadal-Ginard, Bernardo
心力衰竭的流行激发了人们对了解心脏再生的兴趣。已有证据支持通过多种细胞类型的移植以及有丝分裂后心肌细胞的复制来再生。此外，成人心肌含有内源性c-kit（pos）心脏干细胞（eCSCs），其与再生的相关性存在争议。在这里，使用不同的啮齿类动物弥漫性心肌损伤引起急性心力衰竭模型，我们发现eCSCs通过再生失去的心肌细胞来恢复心脏功能。消融术破坏eCSC的再生和功能恢复。用一个eCSC的后代替代消融的eCSC，再生过程完全恢复。从宿主体内恢复并重新克隆的eCSCs在体内和体外均保持其再生潜能。再生后，这些外源性CSCs及其后代的选择性自杀会破坏再生，严重损害心室功能。这些数据表明，c-kit(pos) eCSCs对于心肌损伤的再生和修复是必要和充分的。
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.