| Project/Area Number |
08457302
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
ASAHARA Toshimasa Hiroshima University, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (70175850)
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| Co-Investigator(Kenkyū-buntansha) |
YAHATA Hiroshi Hiroshima University, Medical Hospital, Assistant Professor, 医学部・附属病院, 助教授 (10191181)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | xenogeneic transplantation / biological modulation / microchimerism / bone marrow augmentation / 異種臓器移植 / hamster-to-rat肝移植 / microchimerism / ドナー放射線照射 / recipient骨髄細胞門脈投与 |
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| Research Abstract |
This study was designed to analyze the microcimerism (MC) in the hamster-to-rat xenografted recipients, and to evaluate the effect of donor bone marrow (DBM) augmentation on xenograft survival. We established the method using PCR for detection of MC in hamster-to-rat combination To assess the biological relevance of MC after organ xenotransplantation, both lung and heart recipients were divided into three groups : group I were untreated ; group 2 received short course of cyclophosphamide FK506 ; and group 3 were treated with a long course of immunosuppressants. In these groups, MC changed in parallel with the progression of rejection in lung grafts, whereas it was not detected in heart grafts. In group 3, MC changed dynamically ; once disappeared and then it increased in both organs. This delayed development of MC suggests the existence of donor passenger leukocytes in the recipients that had the character of the hematopoietic stem cells. Hamster DBM (2.OX108) were infused immediately after liver/heart xenotransplanration. Recipients were divided into four groups : group 1 were untreated ; group 2 were infused with DBM ; group 3 received a (liver : FK5O6/heart : cyclophosphamide and FK506) ; and group 4 were infused with DBM and short course of immunosuppressants. In both organs MST for group 4 were significantly longer than that for group 3. The duration of the MC state in the peripheral blood was clearly longer in group 4 thanin group 3 after liver transplantation. In heart group 3, MC was observed in only group 4 continuously until day 30. In conclusion, these findings suggest that concomitant DBM augmentation promoted MC in and markedly prolonged the xenograft survival without long standing immunosuppressive therapy. But in this study, MC was not persistent, and long-lasting graft acceptance could not be achieved. In order to make persistent xenogeneic MC, further studies are required.
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