Background
Fulminant liver failure (FLF) is a life‐threatening disease.
Methods
Lethal FLF was induced by ischemia‐reperfusion (I‐R) injury in mini‐pigs, and MSCs were infused via splenic vein after reperfusion.
Results
Accumulated survival within 28 days was significantly improved by MSCs (P = 0.0348). Notably, MSCs maintained blood‐gas homeostasis in the first 24 hours and prevented FLF‐induced elevation of prothrombin time, international normalized ratio, and creatinine and ammonia levels in the first 3 days. With MSCs, serum levels of liver enzymes gradually decreased after 3 days, and platelet count was back to normal at 1 week of FLF. MSCs promoted liver regeneration within 2 weeks and differentiated into functional hepatocytes at 2‐4 weeks after transplantation, evidenced by increase in Ki67‐positive cells, detectable human hepatocyte growth factor, human vascular endothelial growth factor, human hepatocyte‐specific antigen, and human albumin‐expressing cells in the liver at different time points. Reactive oxidative species (ROS) were accumulated after FLF and eliminated at 4 weeks after MSC transplantation.
Conclusions
Together, MSCs prolong the survival and prevent lethal sequelae of I‐R injury‐induced FLF by maintenance of liver‐function homeostasis and rescue of ROS in the acute stage and by homing and differentiation into hepatocytes in the subacute stage.