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1995 Fiscal Year Final Research Report Summary

Establishment of Transgenic Pig for Organ Xenotransplantation

Research Project

Project/Area Number 06557068
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionNagoya University

Principal Investigator

TAKAGI Hiroshi  Nagoya Univ.School of Med.Professor, 医学部, 教授 (70154755)

Co-Investigator(Kenkyū-buntansha) 小林 章二  愛知県農業総合試験場, 生物工学部, 主任研究員
OKADA H  Med.School, Nagoya City Univ.Prof., 医学部, 教授 (30160683)
NAKASHIMA I  Nagoya Univ.School of Med.Prof., 医学部, 教授 (40022826)
ISOBE K  Nagoya Univ.School of Med.Assoc.Prof., 医学部, 助教授 (20151441)
HAYASHI S  Nagoya Univ.School of Med.Assis.Prof., 医学部, 助手 (30218573)
KOBAYASHI S  Aichi-ken Agricultural Res.Center Senior Res.Scientist
Project Period (FY) 1994 – 1995
KeywordsXenotransplantaion / Transgenic pig / Complement regulatory factor / Xenoantigen / Gene engineering
Research Abstract

In organ xenotransplantetion, 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. Then the construction of transgenic pig with DAF,HRF20, and membrane cofactor protein (MCP) was studied. To control the expression of major xenoantigen GalalphaGal, double knockout of alpha (1,3) GT gene on embryonic stem (ES) cells was examined. As another strategy to control GalalphaGal, it was demonstrated that the transduction of alpha (1,2) FT gene to the xenogenic cell inhibited the GaalphaaGal expression and complement-dependent cytotoxicity, and the transgenic pig with alpha (1,2) FT gene was established. Thus it is concluded that the construction of transgenic pigs with complement regulatory factor genes and alpha (1,2) FT gene is useful for the successful clinical xenotransplantation.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] M.Yasutomi,et al.: "Effect of tetrahydropyranyladriamycin on concordant xenotransplantation in the splenocyte injection and heart transplantation model" Transplantation Proceedings. 27. 1628-1629 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Hayashi,et al.: "Evidence that donor pretreatment with FK506 has a synergistic cffect on graft prolongation in hamster-to-rat heart xenotransplantation" Journal of Heart and Lung Transplantation. 14. 579-584 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Namii,et al.: "Tetrahydropyranyladriamycin with FK506 combination therapy for hamster-to-rat concordant xenotransplantation" Transplantation Proceedings. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C.Koike,et al.: "Function of human DAF and HRF20 in the double transgenic mouse in xenotransplantation" Surgery Today. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Hayashi,et al.: "Effect of antisense ribozyme to pit α(1,3)galactosyl transferase gene on the expression of Gal α(1,3)Gal epitope" Transplantation Proceedings. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高木 弘: "異種移植" 医学のあゆみ. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yasutomi, et al: "Effect of tetrahydropyranyladriamycin on concordant xenotransplantation in the splenocyte injection and heart transplantaion model" Transpl Proc. 27. 1628-1629 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Hayashi, et al: "Evidence that double transfection to xenoendothelial cells using GPI-anchoring complement regulatory factor (DAF and HRF20) genes is useful for the inhibition of human complement-mediated cytolysis" Xenotransplantation. 2. 259-294 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Hayashi, et al: "Evidence that double transfection to xeno-endothelial cells using GPI-anchoring complement regulatory factor (DAF,HRF20) genes is useful for the inhibition of human complement mediated cyrolysis" Transpl Proc. 27. 330 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Hayashi, et al: "Evidence that donor pretreatment with FK506 has a synergistic effect on graft prolongation in hamster-to-rat heart xenotransplantation" J of Heart and Lung Transpl. 14. 579-584 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C.Koike, et al: "How can human DAF and HRF20 prevent hyperacute rejection in transgenic mice?" Transpl Proc. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Namii, et al: "Tetrahydropyranyladriamycin with FK506 combination therapy for hamster-to-rat concordant xenotransplantation" Transpl Proc. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kobayashi, et al: "In vitro and in vivo investigation of the anti-complement agents, FUT-175 and K76COOH,in the prevention of hyperacute rejection following discordant xenotransplantation in a non-human primate model" Transpl Proc. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C.Koike, et al: "Function of human DAF and HRF20 in the double transgenic mouse in xenotransplantation" Surgery Today. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Hayashi, et al: "Effect of antisense ribozyme to pit alpha (1,3) galactosyl transferase gene on the expression of Galalpha (1,3) Gal epitope" Transpl Proc. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Yasutomi, et al: "Establishment of a concordant xenogeneic splenocyte injection model for the dynamic study of the marginal zone in the spleen" J of Heart and Lung Transpl. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C.Koike, et al: "Introduction of alpha (1,2) fucosyltransferase and its effect on alpha-Gal epitopes in transgenic pig" Xenotransplantation. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Hayashi, et al: "Protection of guinea pig cells transfected with 512 gene from complement dependent cytolysis of rat" Transpl Proc. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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