Jung Ji-Hye, Fu Xuebin, Yang Phillip C
From the Stanford Cardiovascular Institute, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA.
Circ Res. 2017 Jan 20;120(2):407-417. doi: 10.1161/CIRCRESAHA.116.309307.
Cardiovascular disease (CVD) is the leading cause of death in modern society. The adult heart innately lacks the capacity to repair and regenerate the damaged myocardium from ischemic injury. Limited understanding of cardiac tissue repair process hampers the development of effective therapeutic solutions to treat CVD such as ischemic cardiomyopathy. In recent years, rapid emergence of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes presents a valuable opportunity to replenish the functional cells to the heart. The therapeutic effects of iPSC-derived cells have been investigated in many preclinical studies. However, the underlying mechanisms of iPSC-derived cell therapy are still unclear, and limited engraftment of iPSC-derived cardiomyocytes is well known. One facet of their mechanism is the paracrine effect of the transplanted cells. Microvesicles such as exosomes secreted from the iPSC-derived cardiomyocytes exert protective effects by transferring the endogenous molecules to salvage the injured neighboring cells by regulating apoptosis, inflammation, fibrosis, and angiogenesis. In this review, we will focus on the current advances in the exosomes from iPSC derivatives and discuss their therapeutic potential in the treatment of CVD.
心血管疾病(CVD)是现代社会的主要死因。成体心脏天生缺乏修复和再生因缺血性损伤而受损心肌的能力。对心脏组织修复过程的有限了解阻碍了治疗CVD(如缺血性心肌病)的有效治疗方案的开发。近年来,诱导多能干细胞(iPSC)和iPSC衍生的心肌细胞的迅速出现为向心脏补充功能细胞提供了宝贵机会。iPSC衍生细胞的治疗效果已在许多临床前研究中得到研究。然而,iPSC衍生细胞疗法的潜在机制仍不清楚,并且iPSC衍生的心肌细胞的有限植入是众所周知的。其机制的一个方面是移植细胞的旁分泌作用。iPSC衍生的心肌细胞分泌的微泡(如外泌体)通过转移内源性分子来发挥保护作用,通过调节细胞凋亡、炎症、纤维化和血管生成来挽救受损的邻近细胞。在这篇综述中,我们将关注iPSC衍生物中外泌体的当前进展,并讨论它们在治疗CVD中的治疗潜力。