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Hepatic endothelial cell function in the assessment of graft viability after liver transplantation and modification of donor MHC antigens by antisense gene transfer to prevent rejection of transplanted organs

Research Project

Project/Area Number 08671411
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionChiba University

Principal Investigator

SHIMIZU Hiroaki  Chiba University, School of Medicine, The First Departrnent of Surgery, Assistant, 医学部, 助手 (80272318)

Co-Investigator(Kenkyū-buntansha) AMBIRU Satoshi  Chiba University, School of Medicine, The First Department of Surgery, Assistant, 医学部, 助手 (30251200)
ITO Hiroshi  Chiba University, School of Medicine, The First Department of Surgery, Assistast, 医学部, 助手 (00232463)
MIYAZAKI Masaru  Chiba University, School of Medicine, The First Department of Surgery, Lecturer, 医学部, 講師 (70166156)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsLivertransplantation / Hepatic Sinusoidal endo thelial cell / MHC antigen / Gene transfection / Antisense DNA / 細織適合性抗原 / アンチセンス
Research Abstract

1.In our first study, we investigated the mechanism of cold ischemia-reperfusion injury, especially the relationship between sinusoidal endothelial cell (SEC) function and graft viability after liver transplantation. According our results, graft failure after cold ischemia-reperfusion primarily resulted from SEC damage, leading to decreased sinusoidal blood flow. Hepatocellular ischemic necrosis might occur secondarily as a result of decreased portal reflow, with eventual graft failure. Therefore, monitoring serum hyaluronic acid for the assessment of SEC function, and hepatic venous oxygen saturation levels for evaluation of hepatic microcirculation after reperfusion might be useful to estimate the prognosis of a graft after liver transplantation.
2.In our second study, we examined whether insertion of an antisense vector into the allograft could down-regulate the expression of the target antigens and to prevent the rejection of transplanted organs. In vitro study, down-regulation of donor MHC class I antigen expression on the donor cells was observed after transfection of plasmid vector containing antisense of donor target antigen in vitro and also immunological response to these cells. However, in vivo, efficient transfection of antisense DNA to the donor graft organ was very difficult at present. Now we are developing new technology to provide for efficient in vivo transfection.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] 清水 宏明 他: "ラット心移植における膜結合型および可溶性分泌型アOMHCクラスI抗原に対する宿主免疫応答の検討" 移植. 31巻4号. 275-284 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroaki Shimizu et al: "Evaluation of early graft function by hepatic venous hemoglobin oxygen saturation following orthetopic liver transplantaion in the rat" Transplantation. Vol.62,No10. 1499-1501 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 清水 宏明 他: "ドナーMHC classI遺伝子をトランスフェクションしたレシピエントT細胞による抹消性トレランスの誘導" 今日の移植. Vol.10,No5. 727-731 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroaki Shimizu et al: "Mechanism of cold ischemia-reperfusion induced graft injury after orthotopic liver transplantation in rats" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 清水 宏明 他: "肝類洞内皮細胞障害よりみた冷保存肝viabilityの評価法とその意義" 今日の移植.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shigeru Yoshioka, Masaru Miyazaki, Hiroaki Shimizu et al.: "Hepatic venous hemoglobin oxygen saturation predicts regenerative status of remnant liver after partial hepatectomy in rats" Hepatology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimizu H., Miyazaki M., Ito H., Nakagawa K., Ambiru S., Nakajima.: "Immunological response to allogeneic membrane-associated and soluble secreted MHC class I antigen in rat cardiac allograft model. (in Japanese)" Jpn J Transplantation. 81. 275-284 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimizu H., Miyazaki M., Ito H., Nakagawa K., Ambiru S., Nakajima N.: "Evaluation of early graft function by hepatic venous hemoglobin oxygen saturation following orthotopic liver transplantation in the rat." Transplantation. 62. 1499-1501 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimizu H., Miyazaki M., Ito H., Nakagawa K., Ambiru S., Nakajima Shirwan H,Cramer DV.: "Syngereic T lymphoma cells expressing donor antigens can induce peripheral tolerance to allografts. (in Japanese)" Transplantation Today. 10. 727-731 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimizu H., Miyazaki M., Ito H., Nakagawa K., Ambiru S., Nakajima N.: "Mechanism of cold ischemia-reperfusion induced graft injury after orthotopic liver transplantation in rats." Hepato-Gastroenterol. (in press). 1997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shimizu H., Miyazaki M., Ito H., Nakagawa K., Ambiru S., Nakajima: "Evaluation of sinusoidal endothelial cell damage after cold ischemia-reperfusion in rat liver transplantation. (in Japanese)" Transplantation Today.(in press). 1997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshioka S., Shimizu H., Miyazaki M., Ito H., Nakagawa K., Ambiru S., Nakajima N.: "Hepatic venous hemoglobin oxygen saturation predicts regenerative status of remnant liver after liver transplantation in rats." Hepatology. (in press). 1997

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 清水宏明 他: "ラット心移植における膜結合型および可溶性分泌型アロMHCクラスI抗原に対する宿主免疫応答の検討" 移植. 31巻4号. 275-284 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroaki Shimizu et.al.: "Evaluation of early gregt fumction by hepatic vemcus hemogiolin oxygen saturatiin follawing orthctopic liuen tianspolantaluin in the nat" Transplantation. vol62,NO.10. 1499-1501 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 清水宏明 他: "ドナーMHC classI遺伝子をトランスフェクションしたレシピエントT細胞による末梢性トレランスの誘導" 今日の移植. vol10,NO.5. 727-731 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroaki Shimizu et.al.: "Methanism of cold ischemia-repenfusion induced graft inijury after arthotopic liven transplantatidn in nats" Hepat-Gastroenterology. (in Press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 清水宏明 他: "肝類洞内皮細胞障害よりみた冷保存肝vialilrtyの評価法とその意義" 今日の移植. (in Press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Shigeru Yoshioka, Masaru Miyazaki, Hiroaki Shimizu et.al: "Hepati vlnrud hemoglolin oxygen satusetim predicts regenerabiue status of remmint liver aften partial lupatectomy in rats" Hepatology. (in Press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 清水宏明 他: "ラット心移植における膜結合型および可溶性分泌型アロMHCクラスI抗原に対する宿主免疫応答の検討" 移植. 31(4). 275-284 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroaki Shimizu et al.: "Evaluation of early graft function by hepatii venous hemogrobin oxygen saturation following arthotopic liver transplantation in the rat." Transplantation. Vol62,No10. 1499-1501 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 清水宏明 他: "ドナMHC classI遺伝子をトランスフェクションしたレシピエントT細胞による抹消性トレランスの誘導" 今日の移植. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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