The harsh microenvironment in infarcted heart accelerates transplanted bone marrow mesenchymal stem cells injury: the role of injured cardiomyocytes-derived exosomes.
The harsh microenvironment in infarcted heart accelerates transplanted bone marrow mesenchymal stem cells injury: the role of injured cardiomyocytes-derived exosomes.
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梗塞心脏恶劣的微环境加速移植骨髓间充质干细胞损伤：受损心肌细胞来源的外泌体的作用
DOI：
10.1038/s41419-018-0392-5
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发表时间：
2018-03-02
影响因子：
9
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Hu M;Guo G;Huang Q;Cheng C;Xu R;Li A;Liu N;Liu S
干细胞疗法可用于修复和再生受损的心脏组织;然而，移植细胞的低存活率限制了其治疗效果。最近，已经提出外泌体通过介导细胞存活和细胞间通讯来调节多个细胞过程。以下研究调查了损伤的心肌细胞来源的外泌体（心脏外泌体）是否影响移植的骨髓间充质干细胞（BMSC）在梗死心脏中的存活。为了模拟心肌细胞或移植的BMSCs在体内遇到的梗死心脏中的恶劣微环境，将心肌细胞条件培养基和从H2 O2处理的心肌细胞培养基中收集的心脏外泌体与BMSCs在体外氧化应激下培养。心肌细胞条件培养液和心脏exosomes明显加速H2 O2诱导的BMSCs损伤，增加caspase-3/caspase-3裂解率和凋亡率，降低Bcl-2/Bax比值和细胞活力。接下来，我们通过转录激活因子样效应核酸酶（TALEN）基因组编辑技术构建Rab 27 a敲除（KO）小鼠模型，探索心脏外泌体在移植BMSCs体内存活中的作用; Rab 27 a是GTP酶家族，在外泌体分泌中起关键作用。将雄性小鼠GFP修饰的BMSC植入Rab 27 a KO和野生型雌性小鼠中与梗死相邻的存活心肌中。所得结果表明，由于Y染色体Sry DNA、GFP mRNA水平和GFP荧光信号强度较高，Rab 27 a KO小鼠梗死心脏中移植的BMSC存活率增加。综上所述，这些发现揭示了受损的心肌细胞来源的外泌体加速了梗死心脏中移植的BMSCs损伤，从而突出了心肌梗死后移植细胞存活的新机制。
Stem cell therapy can be used to repair and regenerate damaged hearts tissue; nevertheless, the low survival rate of transplanted cells limits their therapeutic efficacy. Recently, it has been proposed that exosomes regulate multiple cellular processes by mediating cell survival and communication among cells. The following study investigates whether injured cardiomyocytes-derived exosomes (cardiac exosomes) affect the survival of transplanted bone marrow mesenchymal stem cells (BMSCs) in infarcted heart. To mimic the harsh microenvironment in infarcted heart that the cardiomyocytes or transplanted BMSCs encounter in vivo, cardiomyocytes conditioned medium and cardiac exosomes collected from H2O2-treated cardiomyocytes culture medium were cultured with BMSCs under oxidative stress in vitro. Cardiomyocytes conditioned medium and cardiac exosomes significantly accelerated the injury of BMSCs induced by H2O2; increased cleaved caspase-3/caspase-3 and apoptotic percentage, and decreased the ratio of Bcl-2/Bax and cell viability in those cells. Next, we explored the role of cardiac exosomes in the survival of transplanted BMSCs in vivo by constructing a Rab27a knockout (KO) mice model by a transcription activator-like effector nuclease (TALEN) genome-editing technique; Rab27a is a family of GTPases, which has critical role in secretion of exosomes. Male mouse GFP-modified BMSCs were implanted into the viable myocardium bordering the infarction in Rab27a KO and wild-type female mice. The obtained results showed that the transplanted BMSCs survival in infarcted heart was increased in Rab27a KO mice by the higher level of Y-chromosome Sry DNA, GFP mRNA, and the GFP fluorescence signal intensity. To sum up, these findings revealed that the injured cardiomyocytes-derived exosomes accelerate transplanted BMSCs injury in infarcted heart, thus highlighting a new mechanism underlying the survival of transplanted cells after myocardial infarction.
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影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
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4.3
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DOI：
10.1152/ajpheart.00835.2012
发表时间：
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影响因子：
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作者：
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作者：
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影响因子：
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作者：
Gitler, AD;Lu, MM;Gruber, PJ
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