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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2021, Vol. 11 ›› Issue (01) : 40 -47. doi: 10.3877/cma.j.issn.2095-1221.2021.01.006

所属专题： 文献；

综述

间充质干细胞源性外泌体microRNA在心脏缺血性损伤修复中的研究进展
曹润峰1, 葛俊文1, 方霞2, 沈立1,†()   
  1. 1. 200062　上海交通大学附属儿童医院（上海市儿童医院）心胸外科
    2. 200011　上海交通大学医学院附属第九人民医院组织工程实验室
  • 收稿日期:2020-05-19 出版日期:2021-02-01
  • 通信作者: 沈立
  • 基金资助:
    国家自然科学基金(81371449)

Advances in mesenchymal stem cell-derived exosome microRNA in repair of Cardiac ischemic injury

Runfeng Cao1, Junwen Ge1, Xia Fang2, Li Shen1,†()   

  1. 1. Department of Cardiothoracic Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China
    2. Tissue Engineering Laboratory of the Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China
  • Received:2020-05-19 Published:2021-02-01
  • Corresponding author: Li Shen
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曹润峰, 葛俊文, 方霞, 沈立. 间充质干细胞源性外泌体microRNA在心脏缺血性损伤修复中的研究进展[J]. 中华细胞与干细胞杂志(电子版), 2021, 11(01): 40-47.

Runfeng Cao, Junwen Ge, Xia Fang, Li Shen. Advances in mesenchymal stem cell-derived exosome microRNA in repair of Cardiac ischemic injury[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2021, 11(01): 40-47.

心脏缺血性损伤是危害人类健康的重要原因，过去的干细胞疗法具有重要的功能缺陷，如免疫排斥、致瘤性和输注毒性等问题。大量研究表明，间充质干细胞的主要治疗作用是由旁分泌因子所介导。最新研究发现，间充质干细胞来源的外泌体microRNA从移植的干细胞转移至缺血损伤的心脏细胞，调节细胞的增殖、凋亡、炎症和血管生成。本文对来源于间充质干细胞的外泌体及其内部microRNA在心脏缺血性损伤修复中的分子机制进行综述。

关键词: 外泌体, microRNA, 心脏缺血性损伤, 分子机制

Cardiac ischemic injuryseriously threatens human health. Previous stem cell therapy has following disadvantages, such as immune rejection, tumorigenicity and infusion toxicity. Previous studies showed that the therapy effect of stem cells transplantation is mainly mediated by paracrine factors. Recent studies have found that stem cell-derived exosome microRNAs are transferred from transplanted stem cells to recipient heart cells and can regulate cell proliferation, apoptosis, inflammation and angiogenesis. Here we reviewed the molecular mechanism of exosomes and the internal microRNAs incardiac ischemic injury repair.

Key words: Exosomes, MicroRNA, Cardiac ischemic injury, Molecular mechanism
图1 间充质干细胞源性外泌体microRNA作用于心脏的缺血性损伤修复过程
图2 外泌体microRNA的生物发生过程
图3 间充质干细胞分泌的外泌体microRNA作用于心肌细胞的分子机制
表1 间充质干细胞分泌的外泌体microRNA作用于心肌细胞
外泌体来源 microRNA 分子机制 作用细胞 效应 引文
体外 miR-125b-5p 抑制心肌促凋亡基因p53和BAK1的表达 心肌细胞 抑制心肌细胞凋亡 [23]
体外 miR-486-5p 激活PI3K / AKT途径 心肌细胞 抑制心肌细胞凋亡 [41]
C57BL/6J miR-125b 抑制p53-Bnip3信号传导 心肌细胞 减少梗死心脏的自噬通量 [37]
C57BL/6J miR-214 网格蛋白介导的选择性内吞外泌体miR-214 心肌细胞 抑制心肌细胞凋亡 [39]
C57BL/6J miR-22 抑制甲基CpG结合蛋白2 （Mecp2） 心肌细胞 抑制心肌细胞凋亡 [25]
C57BL/6J miR-378 抑制丝裂原激活的蛋白激酶（MAPK） 心肌细胞 抑制心肌细胞凋亡 [30]
C57BL/6N miR-21 靶向抑制SORBS2和PDLIM5 心肌细胞 保护心肌免受损伤 [31]
C57BL/6 miR-210 以nSMase2依赖性方式增强外泌体的分泌 心肌细胞
内皮细胞		 促进新生血管的形成，抑制心肌细胞的凋亡 [35]
小鼠 miR-21a-5p 下调Peli1、PDPD4、FasL和PTEN凋亡蛋白质表达水平 心肌细胞 抑制心肌细胞凋亡 [24]
小鼠 miR-144 增加P-Akt、P-GSK3β、P-p44/42 MAPK表达 心肌细胞 改善心肌功能并减少梗死面积 [19,38]
大鼠 miR-146a 下调EGR1 心肌细胞 抑制心肌细胞凋亡 [40]
大鼠 miR-24 抑制Bax、caspase-3蛋白的表达 心肌细胞 抑制心肌细胞凋亡 [42]
大鼠 miR-26a 增加GSK3β表达和减少Cx43表达 心肌细胞 恢复电导率并减少心律不齐 [33]
大鼠 miR-19a 靶向PTEN-Akt/ERK信号通路 心肌细胞 抑制心肌细胞凋亡并保持线粒体膜电位 [34]
图4 间充质干细胞分泌的外泌体microRNA作用于非心肌细胞的分子机制
表2 间充质干细胞分泌的外泌体microRNA作用于心脏非心肌细胞
外泌体来源 microRNA 分子机制 作用细胞 效应 引文
小鼠 miR-126 抑制Spred1和PI3KR2的表达，增强VEGF信号通路 内皮细胞 诱导内皮细胞的增殖和迁移 [47]
小鼠 miR-210 抑制Efna3基因 内皮细胞 促进血管生成 [49]
小鼠 miR-132 靶向RASA1 内皮细胞 增强梗塞周围的新血管形成，并增强心脏功能 [54]
大鼠 miR-21 通过PTEN /Akt途径 内皮细胞 增强心脏细胞存活和血管生成 [50]
C57BL/6 miR-21 显著降低PDCD4表达 内皮细胞 减弱内皮细胞凋亡,且增加新生血管密度 [51]
CD-1小鼠 miR-21-5p 通过磷酸酶/tensin同源蛋白/Akt途径 内皮细胞 增强血管生成和心肌细胞存活 [52]
C57BL/6 miR-182 靶向TLR4/NF-κB/PI3K/Akt信号通路抑制TLR4活性 巨噬细胞 促使巨噬细胞M1型向M2型极化，降低炎症水平 [53]
表3 注射不同生物材料递送外泌体
外泌体来源 方法 模型 结果 引文
大鼠内皮祖细胞 注射用透明质酸水凝胶 大鼠心肌梗死 改善血管生成和心脏功能，减少梗死面积 [67,68]
人诱导的多能干细胞来源的心肌细胞 将外泌体封装在胶原蛋白凝胶中，然后进行移植 大鼠心肌梗死 改善心脏功能，减少梗死面积以及心肌细胞凋亡和肥大 [62]
人间充质干细胞 注射用两亲性肽水凝胶 大鼠心肌梗死 改善心脏功能，减少炎症，心脏纤维化和细胞凋亡，并增加血管生成 [63]
大鼠间质干细胞 注射海藻酸盐凝胶 大鼠心肌梗死 减少心肌细胞凋亡，促进新生血管生成以及改善心脏功能 [60]
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