• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The development of xenograft

Research Project

Project/Area Number 05557065
Research Category

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

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionOsaka University

Principal Investigator

SHIRAKURA Ryota  Osaka Univ Med School Professor, 医学部, 教授 (00116047)

Co-Investigator(Kenkyū-buntansha) NAKAGAMI Tatsuyoshi  Research and Development Center, Nippon Meat Products Inc., 中央研究所, 主任
SHIGEHISA Tamotsu  Research and Development Center, Nippon Meat Products Inc., 中央研究所, 副主査
NAKATA Seizoh  Osaka Univ Med School Assistant Professor, 医学部, 助手 (50116068)
SHIMAZAKI Yasuhisa  Osaka Univ Med School Associate Professor, 医学部, 助教授 (60116043)
MATSUDA Hikaru  Osaka Univ Med School Professor, 医学部, 教授 (00028614)
中埜 粛  大阪大学, 医学部, 講師 (70028653)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥20,100,000 (Direct Cost: ¥20,100,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1993: ¥14,800,000 (Direct Cost: ¥14,800,000)
KeywordsXenograft / Complement / Transgenic / DAF (CD55) / MCP (CD46) / CD59 / DAF(CD55) / MCP(CD46) / CD59(MACIF) / transfection / transgenic / C9D / Transfection / nonMHC / CD4+T cell
Research Abstract

We established several swine endothelial cell (SEC) lines, expressing human MCP,DAF,and an MCP/DAF hybrid by transfection of cDNA,and assessed the function of these transfectant molecules on C-mediated cell lysis as an in vitro hyperacute rejection model of swine to human discordant xenograft.
1) DAF is quite effective to protect SEC from C-mediated cell lysis. Especially, over 80% suppression was observed in high expression clone. On the other hand, MCP is also effective in suppressing C activity, but the less efficient as the C3-step regulator than DAF.Hybrid showed approximate 60% of suppression of C-mediated cell lysis. It is more effective than MCP alone clearly, but indistinct from DAF alone because of the difference in the expression rate of transfectant molecules in each clone.
2) CD59 is effective in protection of SEC when it is sufficiently expressed. However, DC59 is not so efficient in protecting SEC membrane from human C attack as DAF,because SEC is lysed at the C5b-8 step of the human complement cascade.
TRANSGENIC
To obtain the transgenic animals expressing human-MCP at high level, several studies concerning the promoter and enhancer have done. We obtained 11 independent lines of MCP transgenic mice lacking just the polyA signal and 5 lines without the entire 3'UT,as assessed by PCR and Southern blotting. While the expression of MCP in mice carrying MCP cDNA with 120bp of 3'UT was minimal, that in mice carrying MCP cDNA without total 3'UT was evident in many organs ; especially in muscle, heart, and pancreas.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report

Research Products

(35 results)

All Other

All Publications (35 results)

  • [Publications] S. Miyagawa: "Test for ability of decay-accelerating factor (DAF,CD55) and CD59 to alleviate complement-mediated damage of xeno-erythrocytes." Scand. J. Immunol.38. 37-44 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Miyagawa: "Prolonging discordant xenograft survival with anticomplement reagents,K76COOH and FUT175." Transplantation. 55. 709-713 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Miyagawa: "Possibility for prevention of hyperacute rejection by DAF and CD59 in xenotransplantation." Transplant. Proc.26. 1235-1238 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Miyagawa: "Effects of transfectant molecules,MCP,DAF,and MCP/DAF hybrid on xenogenic vascular endotherium." Transplant. Proc.26. 1253-1254 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shuji Miyagawa: "Effects of transfected complement regulatory proteins,MCP,DAF,and MCP/DAF hybrid on complement-mediated swine endotherial cell lysis." Transplantation. 58. 834-840 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S. Miyagawa: "Effect of transfected MACIF (CD59) on complement mediated swine endothelial cell lysis,comparing with those of MCP (CD46) and DAF (CD55)." Transplant. Proc.27. 328-329 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 白倉 良太: "移植免疫の現況と展望" 今日の移植. 46. 269-274 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shuji Miyagawa: "C5b-8 Step lysis of swine endothelial cells by human complement and functional feature of CD59." Scand. J. Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S Miyagawa, R Shirakura, G Matsumiya, S Nakata, H Matsuda, M Matsumoto, H Kitamura, and T Seya.: "Test for ability of decay-accelerating factor (DAF,CD55) and CD59 to alleviate complement-mediated damage of xeno-erythrocytes." Scand.J.Immunol.38. 37-44 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S Miyagawa, R Shirakura, G Matsumiya, S Nakata, H Matsuda, M Hatanaka, M Matsumoto, and T Seya.: "Possibility for prevention of hyperacute rejection by DAF and CD59 in xenotransplantation." Transplant.Proc.26. 1235-1238 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S Miyagawa, R Shirakura, H Izutani, G Matsumiya, S Nakata, H Matsuda, K Iwata, S Nagasawa, A Terado, M Matsumoto, and T Seya.: "Effects of transfectant molecules, MCP,DAF,and MCP/DAF hybrid on xenogenic vascular endotherium." Transplant.Proc.26. 1253-1254 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shuji Miyagawa, Ryota Shirakura, Seizoh Nakata, Goro Matsumiya, Hironori Izutani, Hikaru Matsuda, Kazunori Iwata, Atsuko Terado, Misako Matsumoto, Shigeharu Nagasawa, and T Seya.: "Effects of transfected complement regulatory proteins, MCP,DAF,and MCP/DAF hybrid, on complement-mediated swine endotherial cell lysis." Transplantation. 58. 834-840 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Miyagawa, R.Shirakura, G.Matsumiya, N.Fukushima, S.Nakata, H.Matsuda, M.Matsumoto, H.Kitamura, and T.Seya.: "Prolonging discordant xenograft survival with anticomplement reagents, K76COOH and FUT175." Transplantation. 55. 709-713 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Miyagawa, R.Shirakura, S.Nakata, H.Izutani, H.Matsuda, K.Iwata, S.Nagasawa, A.Terado, M.Hatanaka, M.Matsumoto, and T.Seya.: "Efect of transfected MACIF (CD59) on complement mediated swine endothelial cell lysis, compared with those of MCP (CD46) and DAF (CD55)." Transplant.Proc.27. 328-329 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Miyagawa, R.Shirakura, S.Mikata, M.Tanemura, N.Fukushima, H.Matsuda, A.Terado, M.Hatanaka, M.Matsumoto, and T.Seya.: "The functional feature of C5b-8 step lysis of swine endothelial cell transfected CD59." Transplant.Proc.(In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Miyagawa, M.Ikawa, K.Kominami, Y.Yoshimura, H.Tanaka, S.Mikata, R.Shirakura, H.Matsuda, Y.Yanagi, T.Seya, and M.Okabe.: "Difference of expression levels between gene technological product DCYT-MCP (CD46) intact MCP (CD46) in transgenic mice." Transplant.Proc.(In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Miyagawa, R.Shirakura, H.Mastuda, M.Ikawa, M.Okabe, S.Nagasawa, M.Matsumoto, and T.Seya: "In vivo and in vitro studies to prevent hyperacute rejection." Transplant.Proc.(In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shuji.Miyagawa, Shoki Mikata1,4, Ryota Shirakura1, Hikaru Mastuda2, Shigeharu Nagasawa3, Atsuko Terado4, Michiyo Hatanaka4, Misako Matsumoto4, and Tsukasa Seya4.: "C5b-8 step lysis of swine endothelial cells by human complement and functional feature of transfected CD59." Scand J Immunol. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Miyagawa: "Test for ability of decay-accelerating factor(DAF,CD55)and CD59to alleviate complement-mediated damage of xeno-erythrocytes." Scand.J.Immunol.38. 37-44 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Miyagawa: "Prolonging discordant xenograft survival with anticomplement reagents,K76COOH and FUT175." Transplantation. 55. 709-713 (1993)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Miyagawa: "Possibility for prevention of hyperacute rejection by DAF and CD59 in xenotransplantation." Transplant.Proc.26. 1235-1238 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Miyagawa: "Effects of transfectant molecules,MCP,DAF,and MCP/DAF hybrid on xenogenic vascular endotherium." Transplant.Proc.26. 1253-1254 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shuji Miyagawa: "Effects of transfected complement regulatory proteins,MCP,DAF,and MCP/DAF hybrid on complement-mediated swine endotherial cell lysis." Transplantaion. 58. 834-840 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Miyagawa: "Effect of transfected MACIF(CD59)on complement mediated swine endothelial cell lysis,comparing with those of MCP(CD46)and DAF(CD55)." Transplant.Proc.27. 328-329 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S Miyagawa: "Possibility for prevention of hyperacute rejection on by DAF and CD59 in xeno transplantation" Transplant Proc. 26. 1235-1238 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S Miyagawa: "Effocts of Transfectant Molecules,MCP,DAF and MCP/DAF Hybrid on Xenogenic Vascular Endotherium" Transplaut Proc. 26. 1253-1254 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shuji Miyagawa: "Effeds of Transfected Complement Pcgulatory Proteins,MCP,DAF,and MCP/DAF Hybrid,on Compleawt-Mediated Swine Endotherial Cell lysis." Transplantation. 58. 834-840 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Goro Matsumiya.: "Analysis of rejection mechaiuem in the rat to mouse cardiac xenotransplantation irole and characteristics of anti-endothelial cell antibody" Transplautation. 57. 1653-1660 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Goro Matsumiya: "Role of CD4+T cell in the rat to mouse cardiac xenotrans plantation." Transpl Int. 7. 654-659 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Miyagawa: "Effect of transplanted MACIF(CD59)on complement mediated swie endothehal cell lysis,comparing with those of MCP(CD46)and DAF(CD55)" Transplant Proc. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Miyagawa,R.Shirakura,et al.: "EFFECT OF TRANSFECTANT MOLECULES,MCP,DAF,AND MCP/DAF HYBRID ON XENOGENIC VASCULAR ENDOTHELIUM" Transplantation Proccedings. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Miyagawa,R.Shirakura et al.: "POSSIBILITY FOR PREVENTION OF HYPERACUTE REJECTION BY DAF AND CD59 IN XENOTRANSPLANTATION" Transplantation Proccedings. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] S.Miyagawa,R.Shirakura et al.: "Test for Ability of Decay-Accelerating Factor(DAF,CD55)and CD59 to Alleviate Complement-Mediated Damage of Xeno-Erythrocytes" Scand.J.Immunol. 38. 37-44 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] G.Matsumiya,R.Shirakura et al.: "ASSESMENT OF T CELL SUBSETS INVOLVED IN ANTIBODY PRODUCTION AND CELL MEDIATED CYTOTOXICITY IN THE RAT TO MOUSE CARDIAC XENOTRANSPLANTATION" Transplantation Proccedings. (in press). (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] G.Matsumiya,R.Shirakura et al.: "ANALYSIS OF REJECTION MECHANISM IN THE RAT TO MOUSE CARDIAC XENO TRANSPLANTATION:ROLE AND CHARACTERISTICS OF ANTI-ENDOTHELIAL CELL ANTIBODIES" Transplantation. (in press). (1994)

    • Related Report
      1993 Annual Research Report

URL: 

Published: 1993-03-31   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi