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 fate of transplanted hepatocytes, This study used dipeptidyl peptidase IV-deficient F344 rats as recipients to analyse the engraftment and prolif eration of transplanted hepatocytes, Syngeneic hepatocytes were transplante d intrasplenically 24-30 h after induction of liver injury by D-galactosami ne (GalN), Portosystemic shunting was analysed with 99m-Tc-labelled albumin microspheres, GalN-treated rats showed characteristic hepatic necrosis, in flammation, gamma-glutamyl transpeptidase activation, and regenerative acti vity, without increased portosystemic shunting (>99% 99m-Tc activity was in the liver in normal and GalN-treated rats). Transplanted cells entered hep atic sinusoids promptly and were observed in liver plates at 48 h, The numb er of transplanted cells increased in GalN-treated rats by approximately se ven-fold (range two- to 12-fold), along with evidence for DNA synthesis bet ween 3 and 14 days after cell transplantation and greater prevalence of lar ger transplanted cell clusters. These findings indicate that the liver can be safely repopulated in animals with acute liver failure, although the tim e required for regenesis of plasma membrane structures and proliferation in transplanted hepatocytes will need to be considered in developing therapeu tic strategies. Copyright (C) 2000 John Wiley & Sons, Ltd.