Liver xenotransplantation: changes in lipid and lipoprotein concentration after long-term graft survival

Abstract

Background/Aims: Today, scientists devote considerable effort to the study of mechanisms of xenograft rejection, but with liver xenotransplantation (XTx) researchers face the added problem of metabolic incompatibility between species. To date, there have been few studies of molecular xenogeneic interactions, perhaps because little progress has been made in solving immunological problems. This study is an initial analysis of lipoprotein metabolism in a hamster-to-rat hepatic xenotransplantation model. Methods: There were 6 experimental groups ( n=8): (1) male Sprague-Dawley (S.D.) rats (220–280 g); (2) male Golden Syrian hamsters (100–150 g); (3) S.D. rats, “sham” operation with immunosuppression; (4) S.D. rat-to-S.D. rat alloTx; (5) S.D. rat-to-S.D. rat alloTx with immunosuppression; (6) XTx hamster G.S-to-S.D. rat with immunosuppression. Mofetil mycophenolate (25 mg/kg/d) was administered for 14 days and FK506 (0.2 mg/kg/d) for 45 days (groups 3, 5 and 6). After 24 h fasting, animals were sacrificed (day +50 postransplantation) and a complete lipoprotein profile was determined. Serum lipoproteins were subfractioned by ultracentrifugation in density gradient. Results: There was a large increase in serum lipid levels in xenografted rats compared with control rats and allografted rats. Xenografted rats presented a severely altered lipoprotein profile compared with normal rats. Surprisingly, the characterisation of lipoproteins in xenografted rats displayed the same composition as donor animals. Histological study did not show signs of alteration of the hepatic architecture. Conclusions: Since the liver is the main solid organ co-ordinator of metabolic pathways, such as lipid metabolism, hepatic xenotransplantation makes changes in lipid concentrations in the recipient and also changes in lipid compositions of lipoproteins. Hepatic xenotransplantation is not a feasible solution given the organ's metabolic complexity.