Transfusion Of Endothelial Cells With Lentivirus-mediated Expression Of Fas Ligand Prolonged Survival Of Rat Liver Allograft

Background:Immunologically 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.Methods:Based on the multiply-defective lenti-rFasl/puro expression system, constructs were designed that allow endothelial cell-specific and continual expression of FasL. Endothelial cells with expression of Fas L or virus recombinant with Fas L gene are transfused into portal vein of recipient rats during liver transplant surgical operation. With contrasts of groups of rats after liver transplant surgery using regular dose of FK506and with no special treatment, we observe the AST and BIL value and survival days of four groups of rat recipients.Results:The AST and BIL value of cell and virus transfusion group are between FK506and contrast groups.The survival days of cell and virus transfusion group are longer than contrast group and are shorter than FK506group. Conclusion:This in vitro model shows that endothelial cells with expression of Fas L or viruses recombinant with Fas L gene transfusion can presreve liver function and prolong the survival time of liver allografts.