title: Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats.
abstract: 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 transforming growth factor beta1 (TGF-beta1) levels. Group 3 (n = 16) rats 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 were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group 1 anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01). Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta1 levels when compared with sham-transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta1 levels in rats rendered anhepatic.
authors.affiliation: Liver Support Research Laboratory, Burns and Allen Research Institute, Department of Surgery, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Arkadopoulos
authors.forename: H
authors.initials: H
authors.lastname: Lilja
authors.forename: K S
authors.initials: KS
authors.lastname: Suh
authors.forename: A A
authors.initials: AA
authors.lastname: Demetriou
authors.forename: J
authors.initials: J
authors.lastname: Rozga
mesh_terms: D000641:Ammonia / Q000097:blood; D000818:Animals; D002455:Cell Division; D017690:Cell Transplantation; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000097:blood; D008099:Liver / Q000166:cytology*; D008297:Male; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000097:blood; D016042:Transplantation, Heterotopic
chemical_list: D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D000641:Ammonia