1995 Fiscal Year Final Research Report Summary
Study of Xenotransplatation Using Gene Engineering Technique
| 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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| Keywords | Xenotransplantation / Gene Engineering / Complement regulatory factor / Xenoantibody production / Hyperacute rejection |
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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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