Mesenchymal stem cells (MSCs) have been reported possessing therapeutic effects on immunoregulation, tissue repair and regeneration from bench to bedside. Extracellular vesicles (EVs) derived from MSCs could contribute to these progressions via paracrine function, which are considered as a replacement of stem cell-based therapies. However, the efficacy and underlying mechanisms of EVs-based treatment in hepatic ischemia-reperfusion injury (IRI) remain unclear. Here, we demonstrated that human umbilical cord MSC-derived extracellular vesicles (huc-MSC-EVs) could protect against IRI-induced hepatic apoptosis through reducing the infiltration of neutrophils into inflammation microenvironment of hepatic tissue in vivo. Meanwhile, huc-MSC-EVs reduced respiratory burst of neutrophils as well as prevented hepatocytes from oxidative stress-induced cell death in vitro. Furthermore, we identified that MnSOD, an antioxidant enzyme, was rich in huc-MSC-EVs and reduced oxidative stress. Knockdown of MnSOD in huc-MSCs decreased the expression of MnSOD in huc-MSC-EVs and attenuated the antioxidant and anti-apoptosis of capacities of huc-MSC-EVs. In conclusion, these findings provide new clues to reveal the therapeutic effects on hepatic IRI and evaluate the pre-clinical application of of huc-MSC-EVs.

CITATION INFORMATION: Yao J., Cai J., Zheng J., Chen L., Zhang Y., Yang Y. Extracellular Vesicles Derived from Huc-MSCs Alleviate Rat Hepatic Ischemia-Reperfusion Injury by Suppressing Oxidative Stress and Neutrophil Inflammatory Response Am J Transplant. 2017;17 (suppl 3).

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