| Project/Area Number |
05454350
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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 | Nagoya University |
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Principal Investigator |
TAKAGI Hiroshi Nagoya Univ.School of Med.Professor, 医学部, 教授 (70154755)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Hidechika Med.Shool, Nagoya City Univ.Prof., 医学部, 教授 (30160683)
HAYASHI S Nagoya Univ.School of Med.Assis.Prof., 医学部, 助手 (30218573)
ISOBE K Nagoya Univ.School of Med.Assoc.Prof., 医学部, 助教授 (20151441)
NAKASHIMA Izumi Nagoya Univ.School of Med.Prof., 医学部, 教授 (40022826)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Xenotransplantation / Gene Engineering / Complement regulatory factor / Xenoantibody production / Hyperacute rejection / gene engineering / marzinal zone / トランスジェニックマウス |
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| Research Abstract |
In organ xenotransplantation, hyperacute rejection, induced by natural antibody, xenoantigen, and complement, occurs in a few minutes or hours after reperfusion. In this study, based on the in vitro study, in which the double transduction of complement regulatory factors (DAF and HRF20) is more effective than the single transduction on the xenogeneic cells to inhibit complement-dependent cytotoxicity, double transgenic mice with DAF and HRF20 genes were established.
The mechanism of xenoantibody production was analyzed using splenocyte injection model. In xeno-splenocyte injection, marzinal zone of white pulp in the spleen expanded in proportion to the increase of xenoantibody compared to allo- and iso-splenocyte injection models. It was demonstrated that anti-DNA drugs such as Cyclophophamide was useful for the suppresion of xenoantibody production, and anthracycline had a posssible immunosuppressive agent for the clinical xenotransplantation. Thus it is concluded that the gene engineering of xenogenic organs with complemet regulatory factor genes and the use of immunosuppressive drugs are neccesary for the successful clinical xenotransplantation.
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