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Allogeneic hepatocyte transplantation: Contribution of Fas‐Fas ligand interaction to allogeneic hepatocyte rejection
Author(s) -
KAWAHARA TOSHIYASU,
YAGITA HIDEO,
KASAI SHINICHI,
SAWA MASAYUKI,
KATO KAZUYA,
OKUMURA KO,
FUTAGAWA SHUNJI,
MITO MICHIO
Publication year - 1998
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.1998.13.s1.119
Subject(s) - hepatocyte , fas ligand , transplantation , medicine , immunosuppression , immunology , immune tolerance , monoclonal antibody , hepatocyte growth factor , liver transplantation , cancer research , immune system , antibody , biology , apoptosis , receptor , programmed cell death , biochemistry , in vitro
Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyte transplantation has been considered. However, there are two major problems with allogeneic hepatocyte transplantation: protection of transplanted hepatocytes from rejection and stimulation of the rapid proliferation of surviving cells. Without immunosuppression, allogeneic hepatocytes are rapidly rejected within a few days after transplantation, even though it is relatively easy to induce immunotolerance after allogeneic whole liver transplantation. Accordingly, different rejection mechanisms seem to operate after allogeneic hepatocyte transplantation and whole liver transplantation. To overcome the rejection of transplanted hepatocytes, induction of donor‐specific unresponsiveness to graft without compromising the host immune system would be ideal. We previously reported that the Fas‐Fas ligand system plays a critical role in the CD28‐independent pathway of hepatocyte rejection. Therefore, blockade of rejection using CTLA4 immunoglobulin (CTLA4Ig) or anti‐CD80/86 monoclonal antibodies and anti‐FasL monoclonal antibody may prolong the survival of transplanted allogeneic hepatocytes. Furthermore, administration of hepatocyte growth factor (HGF) can promote the proliferation of allogeneic hepatocytes and this may lead to the development of a functioning liver substitute.