The epicardium, previously viewed as a passive outer layer around the heart, is now recognized as an essential component in development, regeneration, and repair. In this review, we explore the cellular and molecular makeup of the epicardium, highlighting its roles in heart regeneration and repair in zebrafish and salamanders, as well as its activation in young and adult postnatal mammals. We also examine the latest technologies used to study the function of epicardial cells for therapeutic interventions. Analysis of highly regenerative animal models shows that the epicardium is essential in regulating cardiomyocyte proliferation, transient fibrosis, and neovascularization. However, despite the epicardium's unique cellular programs to resolve cardiac damage, it remains unclear how to replicate these processes in nonregenerative mammalian organisms. During myocardial infarction, epicardial cells secrete signaling factors that modulate fibrotic, vascular, and inflammatory remodeling, which differentially enhance or inhibit cardiac repair. Recent transcriptomic studies have validated the cellular and molecular heterogeneity of the epicardium across various species and developmental stages, shedding further light on its function under pathological conditions. These studies have also provided insights into the function of regulatory epicardial-derived signaling molecules in various diseases, which could lead to new therapies and advances in reparative cardiovascular medicine. Moreover, insights gained from investigating epicardial cell function have initiated the development of novel techniques, including using human pluripotent stem cells and cardiac organoids to model reparative processes within the cardiovascular system. This growing understanding of epicardial function holds the potential for developing innovative therapeutic strategies aimed at addressing developmental heart disorders, enhancing regenerative therapies, and mitigating cardiovascular disease progression.

中文翻译：

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探索心外膜细胞表面以外的功能。


心外膜以前被视为心脏周围的被动外层，现在被认为是发育、再生和修复的重要组成部分。在这篇综述中，我们探讨了心外膜的细胞和分子组成，强调了它在斑马鱼和蝾螈心脏再生和修复中的作用，以及它在年轻和成年产后哺乳动物中的激活。我们还研究了用于研究心外膜细胞功能以进行治疗干预的最新技术。对高度再生动物模型的分析表明，心外膜对于调节心肌细胞增殖、短暂纤维化和新血管形成至关重要。然而，尽管心外膜具有独特的细胞程序来解决心脏损伤，但仍不清楚如何在非再生哺乳动物中复制这些过程。在心肌梗塞期间，心外膜细胞分泌调节纤维化、血管和炎症重塑的信号因子，从而不同程度地增强或抑制心脏修复。最近的转录组学研究验证了不同物种和发育阶段的心外膜的细胞和分子异质性，进一步阐明了其在病理条件下的功能。这些研究还为调节心外膜衍生信号分子在各种疾病中的功能提供了见解，这可能会带来新的疗法和修复性心血管医学的进展。此外，通过研究心外膜细胞功能获得的见解启动了新技术的开发，包括使用人类多能干细胞和心脏类器官来模拟心血管系统内的修复过程。 对心外膜功能的不断加深的了解有可能开发出创新的治疗策略，旨在解决发育性心脏病、增强再生疗法和减轻心血管疾病的进展。