Exosomes Derived from Adipose Mesenhymal Stem Cells Ameliorate Lipid Metabolism Disturbances Following Liver Ischemia-Reperfusion Injury in Miniature Swine

Abstract

The liver plays a crucial role in regulating lipid metabolism. Our study examined the impact of Exosomes derived from adipose mesenchymal stem cells (ADSCs-Exo) on lipid metabolism following liver ischemia-reperfusion injury (IRI) combined with partial hepatectomy. We developed a miniature swine model for a minimally invasive hemi-hepatectomy combined with liver IRI. In this study, we administered PBS, ADSCs-Exo, and adipose-derived stem cells (ADSCs) individually through the portal vein. Before and after surgery, we evaluated various factors including hepatocyte ultrastructure, lipid accumulation in liver tissue, and expression levels of genes and proteins associated with lipid metabolism. In addition, we measured serum and liver tissue levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (CHOL). TEM and oil red O stain indicated a significant reduction in liver steatosis following ADSCs-Exo treatment, which also elevated serum levels of HDL, LDL, TG, and CHOL. Additionally, ADSCs-Exo have been shown to significantly decrease serum concentrations of HDL, LDL, TG, and CHOL in the liver (p < 0.05). Finally, ADSCs-Exo significantly downregulated lipid synthesis-related genes and proteins, including SREBP-1, SREBP-2, ACC1, and FASN (p < 0.05), while upregulating lipid catabolism-related genes and proteins, such as PPAR-α and ACOX1 (p < 0.05). ADSCs-Exo as a cell-free therapy highlights its therapeutic potential in hepatic lipid metabolism abnormalities.