Abstract：
Ischemic heart diseases remain the leading cause of death globally, and stem cell-based therapy has been investigated as a potential approach for cardiac repair. Due to poor survival and engraftment in the cardiac ischemic milieu post transplantation, the predominant therapeutic effects of stem cells act via paracrine actions, by secreting extracellular vesicles (EVs) and/or other factors. Exosomes are nano-sized EVs of endosomal origin, and now viewed as a major contributor in facilitating myocardial repair and regeneration. However, EV/exosome therapy has major obstacles before entering clinical settings, such as limited production yield, unstable biological activity, poor homing efficiency, and low tissue retention. This review aims to provide an overview of the biogenesis and mechanisms of stem cell-derived EV/exosomes in the process of cardiac repair and discuss the current advancements in different optimized strategies to produce high-yield EV/exosomes with higher bioactivity, or engineer them with improved homing efficiency and therapeutic potency. In particular, we outline recent findings toward preclinical and clinical translation of EV/exosome therapy in ischemic heart diseases, and discuss the potential barriers in regard to clinical translation of EV/exosome therapy.
摘要：
缺血性心脏病仍然是全球死亡的主要原因，基于干细胞的治疗已被研究为心脏修复的潜在方法。由于移植后心脏缺血环境中的存活和植入不良，干细胞的主要治疗作用是通过旁分泌作用，通过分泌细胞外囊泡（EV）和/或其他因子。外泌体是内体起源的纳米级EV，现在被认为是促进心肌修复和再生的主要贡献者。然而,EV/外泌体治疗在进入临床设置之前存在主要障碍，例如有限的产量，不稳定的生物活性，归位效率低，和低组织保留。这篇综述旨在概述干细胞衍生的EV/外泌体在心脏修复过程中的生物发生和机制，并讨论不同优化策略的最新进展，以生产具有更高生物活性的高产EV/外泌体。或使它们具有改进的归巢效率和治疗效力。特别是,我们概述了在缺血性心脏病中EV/exosome治疗的临床前和临床转化的最新发现，并讨论了EV/exosome治疗临床转化的潜在障碍。
