1999 Fiscal Year Final Research Report Summary
ANALYSIS OF TRANSPLANTATION IMMUNOLOGY IN INTRASPLENIC HEPATOCYTE TRANSPLANTATION
| Project/Area Number |
09671272
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | ASAHIKAWA MEDICAL COLLEGE |
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Principal Investigator |
SAWA Masayuki Asahikawa Medical College, Second Dept. of Surgery, Assistant Professor, 医学部, 助手 (70226059)
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| Co-Investigator(Kenkyū-buntansha) |
KASAI Sinichi ASAHIKAWA MEDICAL COLLEGE, SECOND DEPT. OF SURGERY, ASSISTANT PROFESSOR, 医学部, 教授 (40091566)
SAKATA Hiromi ASAHIKAWA MEDICAL COLLEGE, SECOND DEPT. OF SURGERY, ASSISTANT PROFESSOR, 医学部, 助手 (50235157)
ONODERA Kazuhiko ASAHIKAWA MEDICAL COLLEGE, SECOND DEPT. OF SURGERY, ASSISTANT PROFESSOR, 医学部, 講師 (00204264)
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| Project Period (FY) |
1997 – 1999
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| Keywords | INTRASPLENIC HEPATOCYTE TRANSPLANTATION / TRANSPLANTATION IMMUNOLOGY / ADHESION MOLECULE / CD80 / CD86 |
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| Research Abstract |
Hepatocyte transplantation is a potential therapeutic modality for overcoming the shortage of liver donors, and the clinical application of allogeneic hepatocyie 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 refection 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
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