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

doi:10.3877/cma.j.issn.2095-1221.2021.01.006

Abstract

Abstract:

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

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.

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URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2021.01.006

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2021/V11/I01/40

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References 68

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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]

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]

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]

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]

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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