Effect of conditioned medium from adipose derived mesenchymal stem cells on endoplasmic reticulum stress and lipid metabolism after hepatic ischemia reperfusion injury and hepatectomy in swine.

AIMS:Hepatic ischemia reperfusion injury (HIRI) is associated with liver failure after liver transplantation and hepatectomy. Thus, this study aims to explore the effect of conditioned medium from adipose derived stem cells (ADSC-CM) on endoplasmic reticulum stress (ERS) and lipid metabolism after HIRI combined with hepatectomy in miniature pigs. MAIN METHODS:A model of HIRI combined with hepatectomy in miniature pigs was established. The expression of ERS-related proteins and lipid metabolism related genes, as well as triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL), very low density lipoprotein (VLDL) and acetyl-CoA carboxylase 1 (ACC1) level were measured in liver tissues. KEY FINDINGS:Both ADSCs and ADSC-CM could improve the damage in the ultrastructure of hepatocytes. ADSC-CM significantly decreased the protein expression of GRP78, ATF6, XBP1, p-eIF2α, ATF4, p-JNK and CHOP. Oil red O staining revealed that the degree of hepatocyte steatosis was also significantly reduced after treatment with ADSC-CM. In addition, ADSC-CM remarkably decreased TG, TC, HDL and ACC1 level in liver tissues, while enhanced VLDL content. Finally, SREBP1, SCAP, FASN, ACC1, HMGCR and HMGCS1 mRNA expression was also markedly downregulated in liver tissues. SIGNIFICANCE:Injection of ADSC-CM into the hepatic parenchymal could represent a novel cell-free therapeutic approach to improve HIRI combined with hepatectomy injury. The inhibition of ERS and the improvement of lipid metabolism in the hepatocytes might be a potential mechanism used by ADSC-CM to prevent liver injury from HIRI combined with hepatectomy.