Bone Marrow Mesenchymal Stem Cell-Derived Hepatocyte-Like Cell Exosomes Reduce Hepatic Ischemia/Reperfusion Injury by Enhancing Autophagy
Bone Marrow Mesenchymal Stem Cell-Derived Hepatocyte-Like Cell Exosomes Reduce Hepatic Ischemia/Reperfusion Injury by Enhancing Autophagy
复制标题
骨髓间充质干细胞来源的肝细胞样细胞外泌体通过增强自噬减少肝脏缺血/再灌注损伤。
DOI：
10.1089/scd.2019.0194
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发表时间：
2020-02-24
影响因子：
4
通讯作者：
Chen, Zhishui
中科院分区：
文献类型：
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作者：
Yang, Bo;Duan, Wu;Chen, Zhishui
缺血/再灌注（I/R）损伤仍是肝移植中的一个主要问题。I/R会导致炎性细胞因子释放、细胞凋亡和坏死。骨髓间充质干细胞（BM - MSCs）在体内可分化为肝细胞，且当肝细胞受损时，其分化进一步增强。外泌体是细胞间联系的重要介质。最近研究表明，肝细胞外泌体在抑制肝细胞凋亡和促进肝细胞再生方面发挥着关键作用。因此，我们诱导间充质干细胞分化为类肝细胞并提取其外泌体，随后通过尾静脉将外泌体注入小鼠肝脏I/R模型。同时，使用CoCl₂在体外模拟I/R。我们的数据表明，在体内，间充质干细胞来源的类肝细胞外泌体（MSC - Heps - Exo）能有效缓解肝脏I/R损伤，减少肝细胞凋亡，并降低肝酶水平。与体内实验结果一致，体外实验证实外泌体可有效提高肝细胞对缺血的耐受性并减少肝细胞凋亡。因此我们发现，自噬增强可能是外泌体保护肝脏免受I/R损伤的作用机制。这些结果表明，外泌体在肝脏I/R过程中发挥保护作用，利用BM - MSCs诱导分化为肝细胞并提取外泌体，可能通过生物工程提供一种新的临床治疗方法。
Ischemia/reperfusion (I/R) injury remains a major problem in liver transplantation. I/R causes inflammatory cytokine release, apoptosis, and necrosis. Bone marrow-mesenchymal stem cell (BM-MSCs) can differentiate into hepatocytes in vivo, and the differentiation further increases when hepatocytes are damaged. Exosomes are important mediators of cellular connections. More recently, exosomes of hepatocytes have been shown to play a pivotal role in inhibiting hepatocyte apoptosis and promoting hepatocyte regeneration. To this end, we induced MSCs to differentiate into hepatocyte-like cells and extracted their exosomes, and then we injected the exosomes into a mouse hepatic I/R model through the tail vein. At the same time, CoCl2 was used to mimic I/R in vitro. Our data indicated that in vivo, mesenchymal stem cell-derived hepatocyte-like cell exosomes (MSC-Heps-Exo) effectively relieve hepatic I/R damage, reduce hepatocyte apoptosis, and decrease liver enzymes. Consistent with the in vivo results, the in vitro experiments confirmed that exosomes effectively increased hepatocyte tolerance to ischemia and reduced hepatocyte apoptosis. We found that autophagy enhancement may be the mechanism by which exosomes protect the liver from ischemia/reperfusion injury. These results indicated that exosomes play a protective role in hepatic I/R, and the use of BM-MSCs for hepatocyte induction and exosome extraction may provide a new clinical treatment method through bioengineering.