Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft

Adipose-derived mesenchymal stem cells (ADSCs) possess a liver regeneration capacity and immunosuppressive activity and hold promise in autologous cell-based technology. This study aimed to determine whether autologous ADSCs can improve outcomes in the rat reduced size liver transplantation model. Allogeneic 50% orthotopic liver transplantation followed by administration of autologous ADSCs delivered into the portal vein system was conducted in LEW donor rats and BN recipient rats with phosphate buffered solution (PBS) infusion used as the control. Liver grafts and recipient serum were obtained. We assessed histopathology, regeneration, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T cells (Tregs) on postoperative day (POD) 7 and 14. It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival times (median, 24 days). Liver function, as assessed by the levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, as well as liver apoptosis was significantly alleviated in the ADSC group compared with the control group. In addition, ADSC therapy markedly promoted the expression of PCNA in the allograft. Furthermore, levels of interleukin (IL)-10 and transforming growth factor (TGF)-beta 1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that peripheral Tregs had been significantly increased by the infusion of ADSCs. These results demonstrate that implanted autologous ADSCs improve allogeneic reduced size liver allograft outcomes by attenuating acute rejection and reducing inflammatory responses, as well as enhancing liver regeneration.