Allogeneic hepatocyte transplantation in the rat

Abstract

The immune response leading to rejection of transplanted hepatocytes has not yet been addressed in detail. In the study presented, the rate of hepatic repopulation by transplanted hepatocytes in a syngeneic model (donor: DPPIV +/+ F344; recipient: DPPIV−/− F344) was compared to an allogeneic transplantation model (donor rat: Dark Agouti; recipient rat: DPPIV−/− F344). Wildtype donor hepatocytes delivered via portal injection were detected by histochemical staining of DPPIV enzyme activity in the otherwise negative host liver background and quantified by flow cytometry.24 hours after transplantation, single hepatocytes were detected in the recipient liver parenchyma both in the syngeneic and allogeneic model. 5 days post‐transplantation, small clusters of 1‐5 donor hepatocytes were visible in the syngeneic model as compared to still single cells in the allogeneic model. After 3 weeks, in the syngeneic model 1 % of the recipient liver was replaced by donor hepatocytes while no cells were found in the allogeneic model. Depletion of Kupffer cells (KCs), macrophages resident in the liver, by gadolinium chloride did not increase the rate of repopulation in either model. Thus, KCs mediating the early immune response, were not involved in the rejection of allogeneic hepatocytes, but rather T‐cells eliminating transplanted allogeneic hepatocytes during a three weeks period in time.