ALLOGENEIC HEPATOCYTE TRANSPLANTATION - CONTRIBUTION OF FAS-FAS LIGAND INTERACTION TO ALLOGENEIC HEPATOCYTE REJECTION

Hepatocyte transplantation is a potential therapeutic modality for ove rcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, th ere are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppress ion, allogeneic hepatocytes are rapidly rejected within a few days aft er transplantation, even though it is relatively easy to induce immuno tolerance after allogeneic whole liver transplantation. Accordingly, d ifferent rejection mechanisms seem to operate after allogeneic hepatoc yte transplantation and whole liver transplantation. To overcome the r ejection of transplanted hepatocytes, induction of donor-specifrc unre sponsiveness to graft without compromising the host immune system woul d be ideal. We previously reported that the Fas-Fas ligand system play s a critical role in the CD28-independent pathway of hepatocyte reject ion. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA 4Ig) or anti-CD80/86 monoclonal antibodies and anti-Fast monoclonal an tibody may prolong the survival of transplanted allogeneic hepatocytes . Furthermore, administration of hepatocyte growth factor (HGF) can pr omote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute.