The cytokinetic behavior of donor hepatocytes after syngenic hepatocyte transplantation into the spleen.

Abstract

The cytokinetic behavior of isolated hepatocytes transplanted into the spleen of syngenic normal Wistar rats was studied. Hepatocyte transplantation (HTX) was performed by the intrasplenic injection of 10(7) isolated hepatocytes. The proliferation index (PI) of intrasplenic donor hepatocytes was assessed by immunocytochemical visualization of DNA-synthesizing cells after pulse-labeling with bromodeoxyuridine (BrdU), a thymidine analogue. A method for determination of intrasplenic liver mass based on tissue glutamate dehydrogenase content was developed. The spontaneous PI of donor hepatocytes at 12 and at 20 weeks post-HTX amounted to around 3%. A significant increase of intrasplenic liver mass was demonstrated between the 12th and 20th week post-HTX (from 8.1 +/- 0.8% to 10.8 +/- 0.8% of spleen weight, P less than 0.05). After partial hepatectomy (PH) at 12 weeks post-HTX, the PI of liver cells in the spleen showed a transient increase up to about 10%, which rapidly declined to the "spontaneous" level of 3%. However, PH did not cause an additional increase in intrasplenic liver mass. This study shows that continuous mitotic activity of intrasplenic hepatocytes results in an actual increase of liver mass in spleen. Although a short-lived increase of proliferative activity of ectopically grafted hepatocytes was shown to occur after PH in the HTX-treated rat, this procedure did not result in an additional increase of intrasplenic liver tissue.