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. (May 2022)

• Record Type: Journal Article
• Authors: Lu, Tongyu; Zhang, Jiebin; Cai, Jianye; Xiao, Jiaqi; Sui, Xin; Yuan, Xiaofeng; Li, Rong; Li, Yang; Yao, Jia; Lv, Guo; Chen, Xiaoyan; Chen, Haitian; Zeng, Kaining; Liu, Yasong; Chen, Wenjie; Chen, Guihua; Yang, Yang; Zheng, Jun; Zhang, Yingcai
• Is Part Of: Biomaterials. Volume 284(2022)
• Publication Date: 2022-05
• Subjects: Extracellular vesicles -- Mesenchymal stromal cells -- Nanotherapeutics -- Mitochondria transfer -- Neutrophils extracellular traps -- Liver ischaemia-reperfusion injury; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121486
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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 ischaemia–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. Mechanistically, 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 intrahepatic neutrophils and repairing their mitochondrial function, which highlights the therapeutic value of hUC-MSC-EVs for liver IRI.