Transfusion of Endothelial Cells with Lentivirus-Mediated Expression of Fas Ligand Prolonged Survival of Rat Liver Allograft

Abstract

BackgroundImmunologically privileged sites have been shown to express Fas ligand (FasL) and may protect themselves by inducing apoptosis of infiltrating inflammatory cells. We asked whether the Fas/FasL interaction could be used to protect liver allograft from acute rejection. We proposed that endothelial cells that are resistant to Fas-mediated killing could be considered as a vehicle for expression of recombinant FasL. MethodsBased on the lenti-rFasl/puro expression system, constructs were designed that allowed endothelial cell-specific and continual expression of FasL. Endothelial cells with expression of FasL or viruses recombinant with FasL gene were transfused into portal vein of recipient rats during liver transplant surgery. Comparing groups of rats after liver transplant surgery using regular dose of FK506 and with no other treatment, we observed the aspartate aminotransferase and BIL value and survival of four groups of rat recipients. ResultsValues of AST and BIL in the cell and virus transfusion groups were between FK506 and contrast groups. The survival of cell and virus transfusion groups were longer than contrast group and shorter than FK506 group. ConclusionThis in vitro model shows that endothelial cells with expression of FasL or viruses recombinant with FasL gene transfusion can preserve liver function and prolong the survival time of liver allografts.