摘要：BackgroundMarrow mesenchymal stem cells (MSCs), especially bone MSCs (BMSCs), play a vital role in immunomodulation of graft rejection but many shortcomings limit its application. In this study, we aimed to investigate the modulation effect of MSCs from gingiva (GMSCs) on the rejection of rat liver transplantation model and to explore the potential mechanisms.MethodsGMSCs were obtained from human gingival tissues and BMSCs were harvested from Brown Norway (BN) rats. The siRNA that mediated knockdown of Fas ligand (FASL) expression in GMSCs (FASL-/-GMSCs) was transfected using lentivirus plasmid. Rat orthotopic liver transplantation model was established. The rats were divided randomly into four groups: normal saline (NS) group, FASL-/-GMSCs group, BMSCs group, and GMSCs group, all of which were injected the solution via dorsal vein of penis to construct the rat rejection model Graft survival and liver function indexes were measured. The immunological reactions of recipients including immune-cytokines, T-helper type 17 (Th17) and regulatory T cells (Treg) were also evaluated by flow cytometry.ResultsThe graft survival of recipient rats in the GMSCs group was significantly prolonged in comparison with that of the NS, FASL-/-GMSCs and BMSCs group. GMSCs remarkably decreased the levels of AST, ALT and TBIL. As for immune-cytokines, serum levels of IL-2, IFN-γ and Th 17 in recipient rats from the GMSCs group reduced significantly compared with that of other three groups, while increased serum IL-10 and TGF-β expressions as well as peripheral serum Treg were also observed in GMSCs group.ConclusionGMSCs exert immunoprotection on liver transplants by regulating FAS-FASL pathway. The current study firstly provides basis for GMSCs to be used in clinical anti-rejection after liver transplantation.
