Genetic heterogeneity and efficiency of two different methods of adenovirus-mediated gene transfer in a rat liver transplantation model

Purpose:We used recombinant adenoviral vectors for gene therapy in liver transplantation, and investigated the efficacy of gene transfer and expression on the grafts and genetic heterogeneity, with two exogenous gene transfer methods in three different syngeneic rat strains. Methods:We transferred adenoviral vector encoding Escherichia coli beta-galactosidase via a donor tail vein 3 days before transplantation; via a recipient tail vein immediately after grafting; and ex vivo by perfusion and clamping during transplantation. Results:The high efficacy of beta-galactosidase gene transfer and expression was seen in both delivery systems, with 70% positivity for hepatocytes on day 3, which persisted for at least 3 weeks after transplantation. The efficacy of gene transfer and expression was similar in the three strains (DA, Lewis, and PVG). Conclusion:These data suggest that adenovirus-mediated gene transfer delivers effective gene therapy by tail vein injection of a donor or a recipient, or by ex vivo graft perfusion in rat liver transplantation. It is not necessary to consider the differences in the strains. Furthermore, ex vivo graft perfusion is probably more suitable not only for rat liver transplantation but also possibly for future clinical application.