Extracellular vesicles derived from mesenchymal stromal cells as nanotherapeutics for liver ischaemia-reperfusion injury by transferring mitochondria to modulate the formation of neutrophil extracellular traps
Extracellular vesicles derived from mesenchymal stromal cells as nanotherapeutics for liver ischaemia-reperfusion injury by transferring mitochondria to modulate the formation of neutrophil extracellular traps
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间充质基质细胞衍生的细胞外囊泡通过转移线粒体调节中性粒细胞胞外陷阱的形成，作为肝脏缺血再灌注损伤的纳米疗法
DOI：
10.1016/j.biomaterials.2022.121486
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发表时间：
2022-04-18
期刊：
影响因子：
14
通讯作者：
Zhang, Yingcai
中科院分区：
文献类型：
--
作者：
Lu, Tongyu;Zhang, Jiebin;Zhang, Yingcai
作为纳米治疗药物，间充质基质细胞来源的细胞外囊泡（MSC-EV）被认为是全细胞治疗的有效替代方案，并逐渐进入肝脏疾病的临床领域。在这项研究中，在临床样本和动物模型中，肝组织中中性粒细胞胞外陷阱（NET）的形成被证实是肝脏缺血再灌注损伤（IRI）的关键因素。人脐带源性 MSC-EV（hUC-MSC-EV）可能具有减少 NET 形成并随后改善肝脏 IRI 的功能。从机制上讲，我们表明 hUC-MSC-EV 含有转移到肝内中性粒细胞的功能性线粒体。这种效应触发线粒体融合，随后恢复中性粒细胞中的线粒体状态和功能，从而减少 NET 的形成。总的来说，我们的研究结果表明，MSC-EVs通过将功能性线粒体转移到肝内中性粒细胞并修复其线粒体功能，对抑制局部NETs形成发挥纳米治疗作用，这凸显了hUC-MSC-EVs对肝脏IRI的治疗价值。
As nanotherapeutics, mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are considered a potent alternative for whole-cell therapy and are gradually entering the clinical field of liver diseases. In this study, neutrophil extracellular traps (NETs) formation in liver tissue was verified as a critical factor for liver ischae-mia-reperfusion injury (IRI) in both clinical samples and animal models. Human umbilical cord-derived MSC-EVs (hUC-MSC-EVs) might function to reduce the NETs formation and subsequently improve liver IRI. Mecha-nistically, we showed that hUC-MSC-EVs contain functional mitochondria that are transferred to intrahepatic neutrophils. This effect triggers mitochondrial fusion and subsequently restores the mitochondrial status and functions in neutrophils to reduce NETs formation. Collectively, our findings suggest that MSC-EVs exert a nanotherapeutic effect on inhibiting local NETs formation by transferring functional mitochondria to intra-hepatic neutrophils and repairing their mitochondrial function, which highlights the therapeutic value of hUC-MSC-EVs for liver IRI.