Suppression of humoral immunization against encapsulated xenogeneic hepatocytes and prolongation of their function by 2-week cyclosporine treatment in the rat

Background. Xenogeneic liver transplantation may induce immune reactions no t only against the graft Ed liver but also against the proteins that it syn thesizes. We investigated whether 2-week cyclosporine treatment could suppr ess immunization and improve graft function in a xenogeneic hepatocyte tran splantation model. Methods. Free or encapsulated human hepatoma cells (HepG2) were cocultured for 28 days with splenocytes from Lewis rats or implanted for GO days into the peritoneum of Lewis rats. Results. Anti-HepG2 and antialbumin antibodies wet-e detected in the supern atants of rat splenocytes that were concultured with HepG2 cells and in the serum of rats that had undergo ne transplantation with HepG2 cells. Cyclos porine suppressed this antibody production both in vitro and in vivo. Human alpha-GST blood levels, which reflect hepatocyte injury, were low in cyclo sporine-treated animals but high when encapsulated HepG2 cells were transpl anted without cyclosporine therapy. Western blots revealed human albumin fr om day 3 to day 60 in the serum of mts treated with cyclosporine, but not a fter day 30 in untreated mts. Conclusions. Xenogeneic hepatocytes induce a humoral response that impairs their viability and function. A 2-week course of cyclosporine suppresses th is immune response and improves graft function for up to 60 days.