Department of Immunology, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Department, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Atherosclerosis. 2019 Jun;285:1-9. doi: 10.1016/j.atherosclerosis.2019.03.016. Epub 2019 Mar 23.
The stem cell-based therapy has emerged as a promising therapeutic strategy for treating cardiovascular ischemic diseases (CVIDs), such as myocardial infarction (MI). However, some important functional shortcomings of stem cell transplantation, such as immune rejection, tumorigenicity and infusional toxicity, have overshadowed stem cell therapy in the setting of cardiovascular diseases (CVDs). Accumulating evidence suggests that the therapeutic effects of transplanted stem cells are predominately mediated by secreting paracrine factors, importantly, microRNAs (miRs) present in the secreted exosomes. Therefore, novel cell-free therapy based on the stem cell-secreted exosomal miRs can be considered as a safe and effective alternative tool to stem cell therapy for the treatment of CVDs. Stem cell-derived miRs have recently been found to transfer, via exosomes, from a transplanted stem cell into a recipient cardiac cell, where they regulate various cellular process, such as proliferation, apoptosis, stress responses, as well as differentiation and angiogenesis. The present review aimed to summarize cardioprotective exosomal miRs secreted by transplanted stem cells from various sources, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and cardiac stem/progenitor cells, which showed beneficial modulatory effects on the myocardial infracted heart. In summary, stem cell-exosomal miRs, including miR-19a, mirR-21, miR-21-5p, miR-21-a5p, miR-22 miR-24, miR-26a, miR-29, miR-125b-5p, miR-126, miR-201, miR-210, and miR-294, have been shown to have cardioprotective effects by enhancing cardiomyocyte survival and function and attenuating cardiac fibrosis. Additionally, MCS-exosomal miRs, including miR-126, miR-210, miR-21, miR-23a-3p and miR-130a-3p, are found to exert cardioprotective effects through induction of angiogenesis in ischemic heart after MI.
基于干细胞的疗法已成为治疗心血管缺血性疾病（CVID），如心肌梗死（MI）的有前途的治疗策略。然而，干细胞移植的一些重要功能缺陷，如免疫排斥、致瘤性和输注毒性，使干细胞疗法在心血管疾病（CVD）的应用中黯然失色。越来越多的证据表明，移植的干细胞的治疗效果主要是通过分泌旁分泌因子介导的，重要的是，分泌的外泌体中的 microRNAs（miRs）。因此，基于干细胞分泌的外泌体 miR 的新型无细胞治疗可以被认为是治疗 CVD 的一种安全有效的替代干细胞疗法的工具。最近发现，来源于移植干细胞的 miR 通过外泌体从供体细胞转移到受体细胞，在受体细胞中调节各种细胞过程，如增殖、凋亡、应激反应，以及分化和血管生成。本综述旨在总结各种来源的移植干细胞分泌的具有心脏保护作用的外泌体 miR，包括胚胎干细胞（ESCs）、诱导多能干细胞（iPSCs）、间充质干细胞（MSCs）和心脏干细胞/祖细胞，它们对心肌梗死心脏表现出有益的调节作用。总之，干细胞外泌体 miR，包括 miR-19a、mirR-21、miR-21-5p、miR-21-a5p、miR-22、miR-24、miR-26a、miR-29、miR-125b-5p、miR-126、miR-201、miR-210 和 miR-294，通过增强心肌细胞的存活和功能以及减轻心脏纤维化，显示出心脏保护作用。此外，MSCs 外泌体 miR，包括 miR-126、miR-210、miR-21、miR-23a-3p 和 miR-130a-3p，通过在 MI 后缺血性心脏诱导血管生成来发挥心脏保护作用。
