Biodistribution of Intrasplenically Transplanted Hepatocytes in the Rat

ABSTRACT

Liver failure still constitutes a major cause of morbidity and death in patients with liver disease. Various potential treatments have been discussed to reduce liver failure-induced deaths. Recently, interest in hepatocyte transplantation(HT) has markedly increased, and HT has been tried for the treatment of liver failure. Both experimental and clinical data indicate that HT may be beneficial both for the support of an acutely devastated liver and for the correction of genetic disorders resulting in states of metabolic deficiency. For this purpose, the location of the HT has been suggested as a critical point. Therefore, we tried to study the biodistribution of hepatocytes in acute and chronic liver failure model in rats at 2 hours and 24 hours after the injection of 125I-labeled hepatocytes into the spleen. A ninety percent partial hepatectomy model and a dimethylnitrosamine-induced liver-cirrhosis model were used as the acute and chronic liver-failure models respectively. An SV-40 T-transfected immotilized cell line named L2A2 was transplanted intrasplenically. The biodistribution of the transplanted hepatocytes was similar in both the acute and the chronic liver-failure groups. In both groups, the biodistribution studies at 2 hours and 24 hours after intrasplenic transplantation demonstrated that the hepatocytes were localized predominantly in the spleen. However, intrasplenic retention of the transplanted hepatocytes progressively decreased with time. We conclude that methods for preventing the progressive loss of intrasplenic transplanted hepatocytes should be investigated.