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Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats
Author(s) -
Arkadopoulos Nikolaos,
Lilja Helene,
Suh Kyung Suk,
Demetriou Achilles A.,
Rozga Jacek
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280527
Subject(s) - medicine , hepatectomy , liver transplantation , transplantation , saline , viaspan , hepatocyte , hepatocyte growth factor , endocrinology , surgery , chemistry , resection , in vitro , biochemistry , receptor
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 β1 (TGF‐β1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 × 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‐β1 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‐β1 levels when compared with sham‐transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF‐β1 levels in rats rendered anhepatic. (H epatology 1998;28:1365‐1370.)