BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activities in transplantation. This study aimed to determine whether BMMSCs reduce acute rejection and improve outcomes of liver transplantation in rats. METHODS: Orthotopic liver transplantation from Lewis to Brown Norway rats was performed, which was followed by the infusion of BMMSCs through the penile superficial dorsal vein. Normal saline infusion was used as a control. Animals were sacrificed at 0, 24, 72, or 168 hours after BMMSCs infusion. Liver grafts, and recipient serum and spleen tissues were obtained. Histopathology, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T (Treg), Th1, Th2 and Th17 cells were assessed at each time point. RESULTS: BMMSCs significantly attenuated acute rejection and improved the survival rate of allogeneic liver transplantation recipients. Liver enzymes and liver apoptosis were significantly alleviated. The levels of the Th1/Th2 ratio-associated cytokines such as IL-2 and IFN-gamma were significantly reduced and IL-10 was significantly increased. The levels of the Th17/Tregs axis-associated cytokines such as IL-6, IL-17, IL-23, and TNF-alpha were significantly reduced, whereas TGF-beta concentration was significantly increased. Moreover, flow cytometry analysis showed that the infusion of BMMSCs significantly increased Th2 and Treg cells and decreased Th1 and Th17 cells. CONCLUSION: BMMSCs had immunomodulatory effects, attenuated acute rejection and improved outcomes of allogeneic liver transplantation in rats by regulating the levels of cytokines associated with Th1/Th2 and Th17/Treg ratios.
BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activities in transplantation. This study aimed to determine whether BMMSCs reduce acute rejection and improve outcomes of liver transplantation in rats. METHODS: Orthotopic liver transplantation from Lewis to Brown Norway rats was performed, which was followed by the infusion of BMMSCs through the penile superficial dorsal vein. Normal saline infusion was used as a control. Animals were sacrificed at 0, 24, 72, or 168 hours after BMMSCs infusion. Liver grafts, and recipient serum and spleen tissues were obtained. Histopathology, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T (Treg), Th1, Th2 and Th17 cells were assessed at each time point. RESULTS: BMMSCs significantly attenuated acute rejection and improved the survival rate of allogeneic liver transplantation recipients. Liver enzymes and liver apoptosis were significantly alleviated. The levels of the Th1/Th2 ratio-associated cytokines such as IL-2 and IFN-gamma were significantly reduced and IL-10 was significantly increased. The levels of the Th17/Tregs axis-associated cytokines such as IL-6, IL-17, IL-23, and TNF-alpha were significantly reduced, whereas TGF-beta concentration was significantly increased. Moreover, flow cytometry analysis showed that the infusion of BMMSCs significantly increased Th2 and Treg cells and decreased Th1 and Th17 cells. CONCLUSION: BMMSCs had immunomodulatory effects, attenuated acute rejection and improved outcomes of allogeneic liver transplantation in rats by regulating the levels of cytokines associated with Th1/Th2 and Th17/Treg ratios.