Xenotransplantation of hepatocytes in rats with acute liver failure using sirolimus for immunosuppression

Abstract

This study aimed to evaluate the effect of sirolimus (SRL; rapamycin) as an immunosuppressant during xeno transplantation (XT) of rabbit hepatocytes into male Wistar rats with acute liver failure (ALF; n = 72). Isolated rabbit hepatocytes were transplanted intrasplenically into rats within 24 h of chemically induced ALF. Treatment groups received monotherapy with either cyclosporine (CsA) 20 mg/kg or SRL 0.20 mg/kg, or combination therapy with CsA 20 mg/kg + SRL 0.20 mg/kg for 14 days post-transplant. One control group with ALF received no treatment and a second group with ALF received only XT. Surviving rats were euthanized after 14 days, with concurrent blood sampling and organ retrieval for morphological evaluation. Survival rates at 14 days were: no XT/no treatment, 0%; XT alone, 29%; XT + CsA, 79%; XT + SRL, 33%; and XT + CsA + SRL, 33%. Liver morphology showed statistically superior liver regeneration for groups on SRL therapy. It is concluded that, in this hepatocyte XT model, SRL offered no survival advantage for ALF management so CsA still maintains a central role in attempts to develop alternative solutions for ALF.