Integration and proliferation of transplanted cells in hepatic parenchyma following D-galactosamine-induced acute injury in F344 rats

To determine whether liver repopulation with cell transplantation could be of therapeutic value in acute hepatic failure, it is necessary to establish the of transplanted hepatocytes. This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and proliferation of transplanted hepatocytes. Syngeneic hepatocytes were transplanted intrasplenically 24-30 h after induction of liver injury by D- galactosamine (GaIN). Portosystemic shunting was analysed with 99m-Tc- labelled albumin microspheres. GaIN-treated rats showed characteristic hepatic necrosis, inflammation, gamma-glutamyl transpeptidase activation, and regenerative activity, without increased portosystemic shunting (> 99% 99m-Tc activity was in the liver in normal and GaIN-treated rats). Transplanted cells entered hepatic sinusoids promptly and were observed in liver plates at 48 h. The number of transplanted cells increased in GaIN-treated rats by approximately seven-fold (range two- to 12-fold), along with evidence for DNA synthesis between 3 and 14 days after cell transplantation and greater prevalence of larger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the time required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeutic strategies.