The concept that cardiac-derived cKit+ cells can regenerate the injured adult heart by transdifferentiating into functioning cardiomyocytes was proposed 14 years ago although it remains controversial because of negative data from multiple independent laboratories. Irreproducibility of cardiac cKit+ cell studies was attributed to the differences in cell isolation, selection, and expansion before in vivo application. This Viewpoint will discuss recent results that again change the formula for how cardiac cKit+ cells must be isolated and processed to be cardiomyogenic, as well as discuss the uncertain in vivo relevance of cKit+ cells as putative cardiomyocyte-producing stem cells. The regenerative and myogenic potential of cKit+ cardiac-resident stem cells (CSCs) remains a dominant and contentious topic. In vitro expanded cKit+ CSCs were originally described 14 years ago as a source for robust new myocyte generation when injected directly into the adult rodent heart after myocardial infarction,1 and although some laboratories have confirmed the basic principle, the magnitude of the effect remains unclear.2 More recently, Ellison et al3 showed that a clonal cKit+ cell line derived from a population of cardiac CD45− cKit+ cells was capable of widely regenerating isoproterenol-injured adult rodent hearts with abundant new cardiomyocytes, after simple tail vein infusion. However, many independent laboratories reported that adult cardiac-derived cKit+ cells did not generate appreciable new cardiomyocytes when directly injected back into the injured rat or mouse heart.4–7 In addition to controversies surrounding the regenerative potential of injected cKit+ cell formulations, until recently the field has not attempted to directly address if endogenous cardiac cKit+ cells are true cardiomyocyte producing stem cells of meaningful significance.8 …

中文翻译：

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再生心脏 cKit+ 细胞的身份危机

14 年前提出了心脏来源的 cKit+ 细胞可以通过转分化为功能性心肌细胞来再生受伤的成人心脏的概念，尽管由于多个独立实验室的负面数据仍存在争议。心脏 cKit+ 细胞研究的不可重复性归因于体内应用前细胞分离、选择和扩增的差异。该观点将讨论最近的结果，这些结果再次改变了必须如何分离和加工心脏 cKit+ 细胞以产生心肌的公式，并讨论 cKit+ 细胞作为推定的心肌细胞产生干细胞在体内的不确定性。cKit+ 心脏驻留干细胞 (CSC) 的再生和肌原性潜力仍然是一个主要且有争议的话题。体外扩增的 cKit+ CSC 最初在 14 年前被描述为在心肌梗塞后直接注射到成年啮齿动物心脏时产生强大的新肌细胞的来源，1 尽管一些实验室已经确认了基本原理，但效果的大小仍不清楚。 2 最近，Ellison 等人 3 表明，在简单的尾静脉输注后，源自心脏 CD45- cKit+ 细胞群的克隆 cKit+ 细胞系能够广泛再生异丙肾上腺素损伤的成年啮齿动物心脏，并具有大量新的心肌细胞。然而，许多独立实验室报告说，成年心脏来源的 cKit+ 细胞在直接注射回受伤的大鼠或小鼠心脏时不会产生明显的新心肌细胞。