Abstract
Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation.