| Project/Area Number |
05454353
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
MONDEN Morio Osaka University, Department of Surgery II,Professor, 医学部, 教授 (00127309)
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| Co-Investigator(Kenkyū-buntansha) |
永野 浩昭 大阪大学, 医学部・附属病院, 医員
NAKANO Hiroshi Osaka University Hospital, Department of Surgery II,Staff, 医学部・附属病院, 医員
UMESHITA Koji Osaka University, Department of Surgery II,Staff, 医学部, 助手 (60252649)
KIN Toshio Osaka University, Department of Surgery II,Staff, 医学部, 助手 (50205051)
GOTOH Mitsukazu Osaka University, Department of Surgery II,Associate Professor, 医学部, 助教授 (50162160)
NAGANO Hiroaki Osaka University Hospital, Department of Surgery II,Staff
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | Rat / Tolerance / Intraportal injection / Micro-chimerism / PCR / Mitomycin-C / Antigen modification / Oral Tolerance / micro‐chimerism / mitomycin‐C / oral tolerance / PCR / RFLP / mitomycin / 門脈内投 |
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| Research Abstract |
Organ transplantation is a therapeutic modality for endstage organ disease that deserves broader application. However, in order for organ transplantation to gain its full therapeutic potential, complications related to immunosuppression must be resolved. Induction of donor specific unresponsiveness using a safe modality is critical matter for successful organ transplantation. We have examined the potential protocol for inducing donor specific tolerance using intraportal (IP) injection of donor antigen. We have previously shown that injection of donor spleen cells into the portal system on day -10relative to transplantation on day 0 induced a significant prolongation of cardiac allograft survival and produced indefinite survival of hepatic allograft in rats. In this study the mechanism of this prolongation was analyzed in terms of microchimerism of donor cells and graft-versus-host reaction (GVHR). Initially, we developed a method of an RFLP analysis using PCR to detect donor-type DNA i
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n various organs of recipient animals. Microchimerism could be demonstrated in the spleen with this DNA-analysis upto one month after intraportal injection of donor spleen cells. This was also confirmed by the immunohistochemical study using donor class I specific monoclonal antibody. For the next step, it was determined whether GVHR of the remaining cells in the host was involved for inducing prolongation of the allograft survival. Donor SPCs which were treated with irradiation (RT) or mitomycin-C (MMC) were injected intraportally instead of fresh donor cells as a pretreatment. A significant prolongation over the control was observed following injection of either type of the treated donor spleen cells, indicating GVHR was not a significant factor. Interestingly, marked prolongation (90 days over the mean survival time of control animals) was observed following injection of MMC-treated cells. This prolongation was antigen specific. These results indicate that donor specific unresponsiveness can be induced by intraportal injection of MMC-treated donor spleen cells and deserves the further research using big animals to develop a potential protocol for clinical application. Less
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