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Development of bioartificial liver using transgenic pig

Research Project

Project/Area Number 10044270
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

IKAI Iwao  Graduate School of Medicine, KYOTO UNIVERSITY, Lecturer, 医学研究科, 講師 (60263084)

Co-Investigator(Kenkyū-buntansha) SATOH Seiji  Graduate School of Medicine, KYOTO UNIVERSITY, Assistant, 医学研究科, 助手 (00303834)
HIROO Iwata  Institute of Frontier Medical Science, KYOTO UNIVERSITY, Professor, 再生医科学研究所, 教授 (30160120)
YOSHIO Yamaoka  Graduate School of Medicine, KYOTO UNIVERSITY, Professor, 医学研究科, 教授 (90089102)
BLOOM Eda T.  米国食品医薬品管理局, 室長
PLATT Jeffre  メーヨ医科大学, 医学部, 教授
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥10,100,000 (Direct Cost: ¥10,100,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsBioartificial liver / Transgenic pig / Functional evaluation / Bioreactor / ブタ肝細胞培養 / 機能評価
Research Abstract

1. Morpholugical and functional evaluation of transgenic pig liver for artificial liver
Porcine hepatocytes were isolated from normal pigs and human decay accelerating factor (hDAF)-transgenic pigs with collagenase digestion method. The viability of hepatocytes was approximately 90%, and 70-80% after cryopreservation. Exposure of normal and hDAF-transgenic porcine hepatocytes to human complements or human serum did not affect on their morphology and function. On the other hand, normal pig livers cross-circulated directly with healthy baboons were induced liver dysfunction due to endothelial cell injury and -hemolysis by humoral immunoreactions, although hDAF-transgenic pig livers were not.
2. Development of bioreactor for bioartificial liver
A hollow fiber cartridge that has been clinically used for hemodialysis was used for a bioartificial cartridge. The hollow fiber in the cartridge was made of cellulose triacetate with nominal cut-off molecular weight of 70 kDa. The isolated porcine hepatocytes were inoculated into the inner space of hollow fiber. The function of bioreactor inoculated porcine hepatocytes was evaluated by loading chemicals
These chemicals were rapidly eliminated after loading for at least 10 days, and the hepatocyte in the hollow fiber formed well-organized aggregates with re-established tight junction and trabecular like structure.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Hiroo Iwata: "Preparation of bioartificial liver using hollow fibers with four different cut-off molecular eights"Transplant Proc. 32. 107-108 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] David P.Foley: "Bile acids in xenogeneic ex-vivo liver perfusion ; function of xenoperfused livers and compatibility with human bile salts and porcine livers"Transplantation. 69. 242-248 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshikazu Yagi: "Extracorporeal xenoperfusion of the pig liver as a liver assist device ; the effects of prostaglandin El and soluble complement receptor type 1"Transplant Proc. 30. 74-75 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koichi Kinoshita: "Exposure of hepatic sinusoidal mononuclear cells to UW solution in situ but not ex vivo induced apoptosis"J Hepatol. 29. 300-305 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwata H. et al.: "In vitro evaluation of metabolic functions of a bioartificial liver"ASAIO J. 45. 299-306 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akiyoshi Kanazawa: "The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death"J Surg Res. 80. 229-235 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nobuhiko Shinkura: "Autoantibodies to FK506 binding protein 12 (FKBP12) in autoimmune diseases"Autoimmunity. 29. 159-170 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takehiko Uesugi: "Evaluation of ammonia and lidocaine clearance and galactose elimination capacity of xenoperfused pig livers using a pharmacokinetic analysis"Transplantation. 68. 209-214 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Scott L. Nyberg: "Influence of human fulminant hepatic failure sera on endogenous retroviral expression in pig hepatocytes"Liveer Transpl. 6. 76-84 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Charles W. Hoopes: "Screening by tRNA primer extension analysis of porcine kidney mRNA libraries defines a novel endogenous porcine retroviral long terminal repeat"Transplantation. 67. 1391-1395 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshinobu Sajiki: "Morphologic studies of hepatocytes entrapped in hollow fibers of a bioartificial liver"ASAIO J. 46. 49-55 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osamu Takeyama: "The protective role of Kupffer cells in humoral injury of xenoperfused rat liver"Transplantation. 69. 1283-1289 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwao Ikai: "Xenogeneic extracorporeal liver perfusion as a liver assist device"Tissue Engineering for Therapeutic Use. 4. 177-188 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshinobu Sajiki: "Transmission electron microscopic study of hepatocytes in bioartificial liver"Tissue Eng.. 6. 627-640 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshikazu Yagi: "Extracorporeal xenoperfusion of the pig liver as a liver assist device : the effects of prostaglandin E1 and soluble complement receptor type 1"Transplant Proc. 30. 74-75 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Koichi Kinoshita K: "Exposure of hepatic sinusoidal mononuclear cells to UW solution in situ but not ex vivo induced apoptosis"J Hepatol. 29. 300-305 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroo Iwata H: "In vitro evaluation of metabolic functions of a bioartificial liver"ASAIO J. 45. 299-306 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akiyoshi Kanazawa: "The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death"J Surg Res. 80. 229-235 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nobihiko Shinkura: "Autoantibodies to FK506 binding protein 12 (FKBP12) in autoimmune diseases"Autoimmunity. 29. 159-170 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tokehiko Uesugi: "Evaluation of ammonia and lidocaine clearance, and galactose elimination capacity of xenoperfused pig livers using a pharmacokinetic analysis"Transplantation. 68. 209-214 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Scott L. Nyberg: "Influence of human fulminant hepatic failure sera on endogenous retroviral expression in pig hepatocytes"Liver Transpl. 6. 76-84 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Charles W. Hoopes: "Screening by tRNA primer extension analysis of porcine kidney mRNA libraries defines a novel endogenous porcine retroviral long terminal repeat"Transplantation. 67. 1391-1395 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshinobo Sajiki: "Morphologic studies of hepatocytes entrapped in hollow fibers of a bioartificial liver"ASAIO J. 46. 49-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osamu Takeyama: "The protective role of Kupffer cells in humoral injury of xenoperfused rat liver"Transplantation. 69. 1283-1289 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwao Ikai: "Xenogeneic extracorporeal liver perfusion as a liver assist device"Tissue Engineering for Therapeutic Use. 4. 177-188 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshinobu Sajiki: "Transmission electron microscopic study of hepatocytes in bioartificial liver"Tissue Eng. 6. 627-640 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroo Iwata: "Preparation of bioartificial liver using hollow fibers with four different cut-off molecular weights"Transplant Proc. 32. 1107-1108 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] David P. Foley: "Bile acids in xenogeneic ex-vivo liver perfusion : function of xenoperfused livers and compatibility with human bile salts and porcine livers"Transplantation. 69. 242-248 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshinobu Sajiki: "Morphologic Studies of Hepatocytes Entrapped in Hollow Fibers of a Bioartificial Liver"ASAIO J.. 46. 49-55 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwata Hiroo: "In vitro evaluation of metabolic functions of a bioartificial liver"ASAIO J. 45(4). 299-306 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Uesugi Takehiko: "Evaluation of ammonia and lidocaine clearance, and galactose elimination capacity of xenoperfused pig livers using a pharmacokinetic analysis,"Transplantation. 68(2). 209-214 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akiyoshi Kanazawa: "The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death" J Surg Res. 80. 229-235 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroo Iwata: "In vitro evaluation of metabolic function of a bioartificial liver" ASAIO J.(in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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