INTRASPLENIC TRANSPLANTATION OF ALLOGENEIC HEPATOCYTES PROLONGS SURVIVAL IN ANHEPATIC RATS

To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic, Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats ( n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and tra nsforming growth factor beta 1 (TGF-beta 1) levels. Group 3 (n = 16) r ats received intrasplenic injection of isolated hepatocytes (2.5 x 10( 7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic, Group 2, 3, and 4 rats wer e maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Grou p I anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation ). The anhepatic state was associated with a progressive and statistic ally significant rise in blood HGF and TGF-beta 1 levels. Rats that re ceived hepatocyte transplantation before total hepatectomy had a signi ficantly longer survival time than sham-transplanted anhepatic control s (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01), Additionally, at 12 ho urs post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-bet a 1 levels when compared with sham-transplanted controls, In conclusio n, intrasplenic transplantation of allogeneic hepatocytes prolonged su rvival, improved blood chemistry, and lowered blood TGF-beta 1 levels in rats rendered anhepatic.