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Analysis of mechanisms in delayed xenograft and cellular rejection in xenotransplant between human and swine

Research Project

Project/Area Number 11671588
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionFujita Health University

Principal Investigator

SHIROKI Ryoichi  Fujita Health University, Urology, Associate Professor, 医学部, 助教授 (70226330)

Co-Investigator(Kenkyū-buntansha) SASAKI Hitomi  Fujita Health University, Urology, Lecturer, 医学部, 助手 (00319261)
HOSHINAGA Kiyotaka  Fujita Health University, Urology, Professor, 医学部, 教授 (30229174)
名出 頼男  藤田保健衛生大学, 医学部, 教授 (40084561)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsXenotransplantation / Organ Transplantation / Transplant Immunology / Chronic Rejection / Rejection / T細胞 / SCIDマウス / 血管内皮細胞
Research Abstract

Humanized severe combined immunodeficient (SCID) mice, which exhibited human immunological environment, were established by administration of human peripheral blood lymphocytes (PBL). This hu-PBL-SCID mice were also demonstrated to involve functional human lymphocyte and immunoglobulin in their circulation. To display the real xenotransplant circumstances from swine graft to human in mouse, swine mesenteric arterior was applied for direct bypass of abdominal aorta in hu-PBL-SCID. Analysis of recovered xenograft revealed human IgM adherence to inner rim and lymphocytes invasion on the endothelium of the xenograft. By blocking the xenoreactive serological response with immuno-absorption, pathological analysis indicated these lymphocytes belonged to human CD3+CD4+ in staining. Next, we tried to determine the optimal time to see the cellular rejection in the severest condition by changing the recovering time of xenograft. Stable model of the cellular rejection were.however, difficult to es … More tablish due to the interindividual differences. Human lymphocytes were unable to be detected in the invasion into swine arterior xenografts. We also tried to contitute the human xenoreactive cell line in vitro by recovering this xenografts to tissue culture using irradiated pig aortic endothlial cell (PAEC) as stimulator and irradiated original human lymphocytes as feeder. This experiment, however, resulted in impossible condition due to contaminations from grafts.
Recently Dr.Sasaki, one of our colleagues, showed that human NK cells recognized non-expression of HLA-G & E gene in xenograft and played a role in xenograft rejection (Transplantation 67; 31-37 1999). We tried to indicate this evidence in in vivo system using hu-PBL-SCID mice model. Swine arterior xenogarfts transfected with HLA-G & E gene were recovered from hu-PBL-SCID mice, but no suppressive effect of xenoreactive responses were noted in this experoment. One of our manuscripts containing these results were now (in press). Less

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] 白木良一, 星長清隆: "腎移植慢性拒絶反応の病態と治療"泌尿器科紀要. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 白木良一, 星長清隆: "心停止ドナー腎を用いた献腎移植におけるドナー側危険因子"泌尿器外科. 12. 749-753 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiroki R, Hoshinaga K: "Non-immunological risk factors associated with chromic allografts nephropathy post kidney transplantation"Acta Urologica Japonica. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiroki R, Hoshinaga K: "Donor Risk factors of non-heart beating donors for cadaveric kidney transplantation"Japanese Journal of Urological Surgery. 12 (7). 749-753 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 白木良一, 星長清隆: "腎移植慢性拒絶反応の病態と治療"泌尿器科紀要. (未定)(別紙).

    • Related Report
      2001 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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