Time-related efficacy of liver cell isografts in fulminant hepatic failure

Abstract

We and others have reported that dispersed liver cells transplanted into the spleen parenchyma of syngeneic rats remained functional and viable for a long time. This report describes our results with hepatocellular transplantation as a therapeutic method in a model of fulminant hepatic failure (FHF) in the rat. 60 male Sprague-Dawley rats weighing 200-250 g were used. The FHF was reached through an Eck's fistula with 2/3 hepatectomy at the same time. This model produced lethal hepatic failure in a highly reproducible manner. Liver cells were isolated by the collagenase method. 40 X 10(6) hepatocytes suspended in Hanks' balanced salt solution were transplanted into the spleen parenchyma 24 hr before (group 1), at the same time as (group 2), and 24 hr after (group 3) FHF was achieved. Additional sham-operated animals (groups 4 and 5) and a control group (group 6) were used. The hepatocellular transplantation markedly increased the survival of the animals with induced FHF to 80% (group 1) and 60% (group 2)--but not in group 3 (20%),--compared with 10% in the control group. This study shows that dispersed liver cells transplanted into the spleen can provide sufficient support to allow animals with lethal hepatic failure to survive and recover. Nevertheless the efficacy of transplantation is a time-related phenomenon with the FHF induction.