Exosomes from adipose-derived mesenchymal stem cells can attenuate liver injury caused by minimally invasive hemihepatectomy combined with ischemia-reperfusion in minipigs by modulating the endoplasmic reticulum stress response

Aims: Hepatic ischemia-reperfusion injury (IRI) impairs postoperative recovery of liver function after liver resection or transplantation. It is crucial to minimize liver injury during surgery in order to improve patient survival and quality of life. The aim of this study was to explore the therapeutic efficacy of exosomes from adipose-derived mesenchymal stem cells (ADSCs-exo) against hepatectomy combined with IRI injury and compare that with the effect of adipose-derived mesenchymal stem cells (ADSCs).Main method: Minimally invasive hemihepatectomy combined with hepatic IRI was established in minipigs. A single dose of ADSCs-exo, ADSCs or PBS was injected through the portal vein. The histopathological features and function of the liver, and the oxidative stress levels, endoplasmic reticulum (ER) ultrastructure and ER stress (ERS) response were analyzed pre-and postoperatively.Key findings: ADSCs-exo alleviated the histopathological injuries and ultrastructural changes in the ER, and significantly improved ALP, TP and CAT levels. Furthermore, ADSCs-exo treatment also downregulated ERS-related factors such as GRP78, ATF6, IRE1 & alpha;/XBP1, PERK/eIF2 & alpha;/ATF4, JNK and CHOP. The therapeutic ef-fects of ADSCs-exo and ADSCs were similar.Significance: Intravenous administration of a single dose of ADSCs-exo is a novel cell-free therapeutic approach to improve surgery-related liver injury. Our findings provide evidence of the paracrine effect of ADSCs and an experimental basis for treating liver injury with ADSCs-exo instead of ADSCs.