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Development of a Hybrid Artificial Liver for Treatment of Acute and Chronic Liver Failure Patients

Research Project

Project/Area Number 12305053
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field 生物・生体工学
Research InstitutionKyushu University

Principal Investigator

FUNATSU Kazumori  Kyushu University, Graduate School of Engineering, Professor, 大学院・工学研究院, 教授 (80037960)

Co-Investigator(Kenkyū-buntansha) SHIMADA Mitsuo  Kyushu University, Graduate School of Medical Science, Lecture, 大学院・医学研究院, 講師 (10216070)
SUGIMACHI Keizo  Kyushu University, Graduate School of Medical Science, Professor, 大学院・医学研究院, 教授 (00038762)
NAKAZAWA Kohji  Kyushu University, Graduate School of Engineering, Research Associate, 大学院・工学研究院, 助手 (00304733)
KAJIWARA Toshihisa  Kyushu Institute of Technology, Faculty of Engineering, Associate Professor, 工学部, 助教授 (10194747)
SHIRABE Ken  Kyushu University, Graduate School of Medical Science, Research Associate, 大学院・医学研究院, 助手 (70264025)
井嶋 博之  九州大学, 大学院・工学研究院, 助教授 (10274515)
田中 真二  九州大学, 大学院・医学研究院, 助手 (30253420)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥38,680,000 (Direct Cost: ¥34,900,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2001: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2000: ¥22,300,000 (Direct Cost: ¥22,300,000)
KeywordsHybrid Artificial Liver / Preclinical Study / Acute Liver Failure / Chronic Liver Failure / Polyurethane Foam / Hepatocyte Spheroid / Hollow Fiber / Hepatocyte Organoid / 肝小葉類似構造 / 遠心力 / ポリウレタン発泡体 / ラット実験 / 血管網類似構造 / 免疫反応
Research Abstract

1. Development of a hybrid artificial liver for clinical trial
We developed a hybrid artificial liver (HAL) which consists of a hepatocyte culture module with multi-capillary polyurethane foam packed-bed containing 200 g primary porcine hepatocytes and an extracorporeal circulation line. Almost all of the hepatocytes in the module formed spheroids, and they maintained the liver specific functions for at least 2 weeks. As preclinical study, the HAL was applied to about 25 kg warm ischemic liver failure pigs. In the preclinical study, we demonstrated its effectiveness such functions as suppression of increase of blood ammonia, maintenance of blood glucose, stabilization of vital sign and urinary excretion, extension of survival time. The HAL was effective to stabilize the general conditions of the body in addition to supporting various liver functions. These results suggest that the HAL has a strong possibility to be used in treating acute liver failure patients.
2. Development of novel hybrid artificial liver module using hepatocyte organoid culture
As a novel artificial liver module, we developed a hollow fiber module having a liver lobule-like structure, in which the hollow fibers representing blood vessels are arranged by spacers in a micro-regular arrangement within 150 μm. Inoculated hepatocytes in the extra-fiber space were formed in a lotus root-organoid by loading appropriate centrifugal force. The novel module achieved high cell density of about 4.0 x l0^7 cells / cm^3 - module and maintained better liver function compared to previous hollow fiber modules for several month. These results suggest that this novel module will be a new HAL for treatment of both chronic and acute liver failure patients, and for long-term bridge use for liver transplantation. Now we are investigating the optimization and scale up of the module.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] H.Iijima: "Development of a hybrid artificial liver support system and preclinical animal experiments"Journal of Artificial Organs. 3(2). 112-116 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y.Fujii: "Intensive promotion of spheroid formation by soluble factors in a hepatocyte-condition medium"Journal of Biomaterials Science Polymer Edition. 17(7). 731-745 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Funatsu: "Hybrid artificial liver using hepatocyte organoid culture"Artificial Organs. 25(3). 194-200 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] J.Fukuda: "Mass preparation of primary porcine hepatocytes and the design of a hybrid artificial liver module using spheroid culture for a clinical trial"The International Journal of Artificial Organs. 24(11). 799-806 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Funatsu: "Editorial review-Novel hybrid artificial liver using hepatocyte organoids"The International Journal of Artificial Organs. (In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Nakazawa: "Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment"The International Journal of Artificial Organs. 25(In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 船津和守: "技術予測レポート3巻:医療・健康・高齢者社会への対応技術編"日本ビジネスレポート. 13 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Ijima: "Development of a hybrid artificial liver support system and preclinical animal experiments"Journal of Artificial Organs. 17(7). 112-116 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Fujii: "Intensive promotion of spheroid formation by soluble factors in a hepatocyte-condition medium"Journal of Biomaterials Science Polymer Edition. 17(7). 731-745 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Funatsu: "Hybrid artificial liver using hepatocyte organoid culture"Artificial Organs. 25(3). 194-200 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Yamashita: "The Efficacy of Nafamostat Mesilate on the Performance of a Hybrid Artificial Liver Using a Polyurethane Foam/Porcine Hepatocyte Spheroid Culture System In Human Plasma"The International Journal of Artificial Organs. 24(1). 34-40 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] J. Fukuda: "Mass preparation of primary porcine hepatocytes and the design of a hybrid artificial liver module using spheroid culture for a clinical trial"The International Journal of Artificial Organs. 24(11). 799-806 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y. Yamashita: "Polyurethane Foam / Spheroid Culture System Using Human Hepatoblastoma Cell Line (Hep G2) as a Possible New Hybrid Artificial Liver"Cell Transplantation. 10. 717-722 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Funatsu: "Editorial review -Novel hybrid artificial liver using hepatocyte organoids"The International Journal of Artificial Organs. (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] K. Nakazawa: "Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment"The International Journal of Artificial Organs. (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] K.Funatsu: "Hybrid artificial liver using hepatocyte organoid culture"Artificial Organs. 25(3). 194-200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中澤浩二: "PUF/スフェロイド人工肝の倫理委員会申請と問題点"組織培養工学. 27(4). 148-151 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] J.Fukuda: "Mass preparation of primary porcine hepatocytes and the design of a hybrid artificial liver module using spheroid culture for a clinical trial"The International Journal of Artificial Organs. 24(11). 799-806 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 船津和守: "人工肝臓の設計"日本設計工学会誌. 36(8). 231-238 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Funatsu: "Editorial review -Novel hybrid artificial liver using hepatocyte organoids"The International Journal of Artificial Organs. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Nakazawa: "Development of a hybrid artificial liver using polyurethane foam/hepatocyte spheroid culture in a preclinical pig experiment"The International Journal of Artificial Organs. 25(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 中澤浩二: "ヒト臨床用ハイブリッド型人工肝臓補助システム-九州大学倫理委員会への申請-"日本機械学会誌. 103巻979号. 364-365 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 福田淳二: "ハイブリッド型人工肝臓"医学のあゆみ. 195巻3号. 188-192 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中澤浩二: "ハイブリッド型人工肝臓と人工膵臓の発展"バイオサイエンスとインダストリー. 58巻11号. 777-780 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.FUJII: "Intensive Promotion of Spheroid Formation by Soluble Factors in a Hepatocyte-condition Medium"Journal of Biomaterials Science Polymer Edition. 11巻7号. 731-745 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.IJIMA: "Development of a Hybrid Artificial Liver Support System and Preclinical Animal Experiments"Journal of Artificial Organs. 3巻2号. 112-116 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.FUNATSU: "Hybrid Artificial Liver Using Hepatocyte Organoid Culture"Artificial Organs. 25巻(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 船津和守: "バイオミメティックスハンドブック"エヌ・ティー・エス社. 6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 船津和守: "技術予測レポート3巻:医療・健康・高齢化社会への対応技術編"日本ビジネスレポート社. 13 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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