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Development of bioartificial liver using human hepatocytes

Research Project

Project/Area Number 09557105
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Digestive 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) SAWASAKI Yoshio  National Defense Medical College, KYOTO UNIVERSITY, Associate Professor, 医学部, 助教授 (90092410)
IWATA Hiroo  Institute of Frontier Medical Science, KYOTO UNIVERSITY, Professor, 再生医科学研究所, 教授 (30160120)
YAMAOKA Yoshio  Graduate School of Medicine, KYOTO UNIVERSITY, Professor, 医学研究科, 教授 (90089102)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥5,800,000 (Direct Cost: ¥5,800,000)
KeywordsBioartificial liver / Human hepatocyte / Porcine hepatrocyte / Functional evaluation / Bioreactor / ハイブリッド型人工肝臓 / ヒト肝細胞培養 / ブタ肝細胞培養
Research Abstract

1. Long-term culture of porcine and human hepatocytes and their morphological and functional evaluation
To develop a bioartificial liver using human hepatocytes, we evaluated a new culture method for long-term culture of human hepatocytes.
Porcine hepatocytes were isolated from normal pigs with collagenase digestion method. Their viability was approximately 90 % after isolation and 70-80% after cryopreservation. These porcine hepatocytes were able to be cultured with modified culture medium in which fibroblasts were not proliferated for 3 months, maintaing high cytochrome p450 activity Human hepatocytes isolated from human liver by collagenase-dispase digestion method were cultured with modified culture medium. These cells were confirmed as hepatocytes morphologically 2 months later. These hepatocytes preserved hepatocyte-specific functions 3 months later, in spite of a decrease of cell number and a few cells were observed to proliferate in an early phase.
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 the hollow fibers. The function of bioreactor inoculated porcine hepatocytes was evaluated by loading chemicals such as ammonia, lidocaine, and galactose. These chemicals were eliminated after loading for at least 10 days, and the hepatocyte in the hollow fibers formed well-organized aggregates with reestablished tight junction and trabecular like structure.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Seiji Satoh: "Humoral injury in xenoperfused porcine livers with human whole blood"Transplantation. 64. 1117-1123 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshikazu Yagi: "The protective effects of prostaglandin El on sinusoidal endothelial cells in xenogeneic pig liver perfusion"J Surg Res. 71. 28-34 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kimiki Takahashi: "Increased secretion of urokinase-type plasminogen activator by human lung microvascular endothelial cells"Am J Physiol. 275. L47-L54 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuhiro Kawai: "Inamoto T. Hepatocyte growth inhibitory factor derived from HTLV-I (+) T-cell line is identical to IL-6"Leuk Res. 23. 489-497 (1999)

    • 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] Hiroo Iwata: "In vitro evalution of metabolic functions of a bioartifical 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] Tokehiko Uesugi: "Evaluation of ammonia and lidocame 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] Toshinobu Sajiki: "Morphologic studies of hepatocytes entrapped in hollow fibers of a bioartificial liver"OJ. 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] Toshinobu Sajiki: "Transmission electron microscopic study of hepatocytes in bioartifical 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] Hiroo Iwata: "Preparation of bioartificial liver using hollow fibers with four different cutt-off molecular weights"Transplant Proc. 32. 1107-1108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Seiji Satoh: "Humorak injury in xenoperfused porcine livers with human whole blood"Transplantation. 64. 1117-1123 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toshikazu Yagi: "The protective effects of prostaglandin E1 on sinusoidal endothelial cells in xenogeneic pig liver perfusion"J Surg Res. 71. 28-34 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kimiki Takahashi: "Increased secretion of urokinase-type plasminogen activator by human lung microvascular endothelial cells"Am J Physiol. 275(1 Pt 1). L47-54 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yasuhiro Yasuhiro: "Hepatocyte growth inhibitory factor derived_from HTLV-I(+) T-cell line is identical to IL-6"Leuk Res. 23. 489-497 (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: "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 Twata: "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] Takehiko Uesugi: "Evaluation of ammonia and lidocaine clearance, and galactose elimination capacity of xenoperfused pig livers using a phannacokinetic 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] 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(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Osamu Takeyama: "The protective role of Kupffer cells in Immoral 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] Roshinobu Sajiki: "Transmission electron microscopic study 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] Osamu Takeyama: "The protective role of Kupffer cells in humoral injury of xenoperfused rat liver"Transplantation. (in press).

    • Related Report
      1999 Annual Research Report
  • [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)

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

    • Related Report
      1999 Annual Research Report
  • [Publications] Toshinobu Sajiki: "Morphologic studies of hepatocytes entrapped in hollow fibers of a bioartificial liver"ASAIO J.. 46(1). 49-55 (2000)

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

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroo Iwata et al.: "In vitro evaluation of evaluation of metabolic function of a bioartifical liver." ASAIO J.(発表予定). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Seiji Satoh: "Humoral injury in porcine livers perfuse with human whole blood" Transplantation. 64・8. 1117-1123 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toshikazu Yagi: "The protective effects of prostaglandin E1 on sinusoidal endothelial cells in xenogeneic pig liver perfusion" Journal of Surgical Research. 73・1. 28-34 (1997)

    • Related Report
      1997 Annual Research Report
  • [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" Transplantation Proceedings. 30. 74-75 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kimiko Takahashi: "Increased secretion of urokinase type plasminogen activator by human lung microvascular endothelial cells" American Journal of Physiology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Koichi Kinoshita: "Exposure of hepatic sinusoudal mononuclear cells to UW solution in situ but not ex vivo induced apoptosis" Journal of Hepatology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwao Ikai: "Surgical intervention for patients with Stage IV-A hepatocellular carcinoma without lymph node metastasis" Annals of Surgery. (in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2018-02-02  

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