Heart failure is a significant source of morbidity and mortality around the world. Recently, cell therapy has garnered much attention as a means for improving cardiac function after injury. Despite years of study, a growing list of failed efficacy trials has led many to question the translatability of preclinical work. In this review, we critically evaluate the evidence supporting the need for transplanted cells to engraft and persist in the impaired heart (the cell engraftment hypothesis). We explore how the complex interplay between cell retention, persistence and paracrine potency explains many of the recent cell treatment outcomes. Through this discussion, we outline a framework to understand how future approaches will optimize and personalize the methods, payloads and timing of cardiac cell delivery for the millions of patients worldwide suffering from heart failure.

心力衰竭是全世界发病率和死亡率的重要来源。最近，细胞疗法作为一种改善损伤后心脏功能的手段而备受关注。尽管进行了多年的研究，但越来越多的失败功效试验导致许多人质疑临床前工作的可译性。在这篇综述中，我们批判性地评估了支持移植细胞需要移植到受损心脏中并持续存在的证据（细胞移植假说）。我们探讨了细胞保留、持久性和旁分泌效力之间复杂的相互作用如何解释最近的许多细胞治疗结果。通过这次讨论，我们概述了一个框架，以了解未来的方法将如何优化和个性化方法，