Hepatocellular Transplantation into the Lung in Chronic Liver Failure following Bile Duct Obstruction in the Rat

Abstract

Injection of hepatocytes or cell-free supernatant into the lung was able to prevent death from surgically induced fulminant hepatic failure in the rat in over 90% and 53% of subjects, respectively. The aim of this study was to investigate whether this technique can be applied in chronic liver failure. Chronic liver failure was induced in Lewis rats by ligation and transection of the common bile duct, which led to cirrhosis after 3-5 wk in all animals. Four groups of animals were formed: group 1 (n = 5), normal rats, serving as control; group 2 (n = 15), cirrhotic rats, no further treatment; group 3 (n = 14), hepatocyte transplantation by injection of cell suspension transcutaneously into the right lung of cirrhotic animals four wk after bile duct ligation; group 4 (n = 17), injection of 1 mL cell-free supernatant intravenously at two-day intervals, starting 4 wk after ligation. Liver function tests, prothrombin time and serum protein levels were measured weekly before and every two days after transplantation. In group 2 all animals had died 56 (49-69) days after ligation. Survival in groups 3 and 4 was similar: all rats had died from liver failure 61 (51-72) and 60 (49-76) days following bile duct ligation. Survival rates and laboratory investigations showed no significant differences between treated and untreated cirrhotic animals. These data suggest that hepatocyte transplantation into the lung as well as supernatant injection do not have any significant effect on chronic hepatic failure, at least in the rat model.