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Development of a hybrid artifical liver using PUF/three dimensional culture of normal hepatocytes

Research Project

Project/Area Number 04555225
Research Category

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

Allocation TypeSingle-year Grants
Research Field 化学工学
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

FUNATSU Kazumori  Kyushu Univ. Dept.Chem.Eng. Prof., 工学部, 教授 (80037960)

Co-Investigator(Kenkyū-buntansha) OMOTO Mitsuru  INOAC Technical Center R&D Manager, 主任研究員
MATSUSHITA Taku  Kyushu Univ. Dept.Chem.Eng. Res.Assoc., 工学部, 助手 (10209538)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥16,200,000 (Direct Cost: ¥16,200,000)
Fiscal Year 1993: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1992: ¥8,900,000 (Direct Cost: ¥8,900,000)
KeywordsPolyurethane foam / Hepatocyte Spheroid / Three dimensional culture / Multi-Capillary PUF packed-bed / Hepatic failure rat / Ammonia detoxification / Extracorporeal circulation system / Hybria Artificial liver / 正常肝細胞 / 多細管型PUF充填層 / 生体外組織構築 / プロテオグリカン / 細胞分化機能発現
Research Abstract

1. We designed a prototype of hybrid artificial liver module using optimum polyurethane foam (PUF) material for spheroid formation of hepatocyte in vitro. The module was type of packed-bed with PUF plates (1.5X40X40mm) which immobilized spheroids. In serum-free medium supplemented with 1mM NH_4Cl as a toxic substance, this module detoxified ammonia and synthesized urea from ammonia. The urea synthesis rate of hepatocyte in the module was slightly higher than that of hepatocyte in vivo and was maintained for about 3 weeks.
2. We also developed Multi-Capillary PUF packed-bed for increasing a cell density and achieving an efficient mass transfer, in which a cylindrical PUF block with many capillaries for medium flow was packed. Consequently, a high cell density of 1X10^7cells/cm^3-PUF was achieved and hepatocyte/spheroids were formed in the module. The urea synthesis rate of the module was 10 times higher than that of prototype module.
3. A volume of the hybrid artificial liver module containing 1/10 amount of human liver hepatocytes was estimated to be about 2 liter by using the Multi-Capillary PUF packed-bed. This volume seemed to be a medically applicable value.
4. We developed an extracorporeal circulation system for acute hepatic failure rat to investigate the performance of the artificial liver module in ex vivo experiment. The ammonia concentration in blood increased by actute failure was gone down to normal level by the artificial liver for 3 hour circulation and the hepatic failure rat was recovered.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 井嶋博之: "初代肝細胞のPUF/スフェロイド培養系を用いたハイブリッド型人工肝臓の開発 -アンモニア処理能力の評価-" 人工臓器. 22. 171-176 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松下 琢: "ポリウレタンフォームと三次元培養" 組織培養. 19. 332-335 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 船津和守: "ハイブリッド型人工肝補助システムの開発" 第71期日本機械学会全国大会講演論文集. A. 274-276 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 船津和守: "ハイブリッド型人工肝臓の開発をめざして" バイオインダストリー. 10. 26-32 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "High density culture of animal cells and its application to hybrid artificial liver support systems in Japan" Artificial Organs Today. 4(発表予定). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松下 琢: "初代肝細胞のPUF/スフェロイド培養系を用いたハイブリッド型人工肝臓の開発 -血漿中での肝機能の維持-" 人工臓器. 23(発表予定). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松下 琢: "バイオプロセスシステム工学 -第6章 動物細胞培養-" 株式会社アイピーシー, 500 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hiroyuki Iijima: "Development of a hybrid type artificial liver using PUF/spheroid culture system of adult hepatocyte -Evaluation of ammonia metabolizing activity-" Jpn.J.Artif.Organs. 22. 171-176 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Taku Matsushita: "Three Dimensional Culture of mammalian cells using polyurethane foam as a culture substratum" The Tissue Culture. 19. 332-335 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Development of a hybrid artificial liver support system" The 71st Jpn.Soc.Mech.Eng. Fall Annual Meeting Proc.A. 274-276 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "A trial of development of a hybrid artificial liver" BIO INDUSTRY. 10. 692-698 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "High density culture of animal cells and its application to hybrid artificial liver support systems in Japan" Artificial Organs Today. 4 (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Taku Matsushita: "Development of a hybrid type artificial liver using PUF/spheroid culture system of adult hepatocytes -Estimation of hepatic functions in blood plasma-" Jpn.J.Artif.Organs. 23 (in press). (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Taku Matsushita: "Animal cell culture" I.P.C.INC.Co., Bioprocess System Engineering. Chapter 6. 500(221-254) (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 井嶋博之: "初代肝細胞のPUF/スフェロイド培養系を用いたハイブリッド型人工肝臓の開発 -アンモニア処理能力の評価-" 人工臓器. 22. 171-176 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松下 琢: "ポリウレタンフォームと三次元培養" 組織培養. 19. 332-335 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 船津和守: "ハイブリッド型人工肝補助システムの開発" 第71期日本機械学会全国大会講演論文集. A. 274-276 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 船津和守: "ハイブリッド型人工肝臓の開発をめざして" バイオインダストリー. 10. 26-32 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kazumori Funatsu: "High density culture of animal cells and its application to hybrid artificial liver support systems in Japan" Artificial Organs Today. 4(発表予定). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松下 琢: "初代肝細胞のPUF/スフェロイド培養系を用いたハイブリッド型人工肝臓の開発 -血漿中での肝機能の維持-" 人工臓器. 23. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松下 琢: "バイオプロセスシステム工学 -第6章 動物細胞培養-" 株式会社アイピーシー, 500 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松下 琢: "肝実質細胞のポリウレタンフォーム孔内三次元培養法を利用したハイブリッド型人工肝臓の開発" 人工臓器. 21. 1050-1054 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 松下 琢: "壁付着性動物細胞の高密度培養法に関する研究" 化学工学. 56. 385-386 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kazumori Funatsu: "Hybrid Artificial Liver Undergoing Testing" Medical Equipment Journal of Japan. 36. 10- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 船津 和守: "肝細胞培養装置ー人工肝臓の開発を目指してー" 遺伝. 47. 85-90 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 井嶋 博之: "初代肝細胞のPUF/スフェロイド培養系を用いたハイブリッド型人工肝臓の開発ーアンモニア処理能力の評価ー" 人工臓器. 22. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Taku Matsushita: "BIOCHEMICAL ENGINEERING FOR 2001" Springer-Verlag, 847 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hiroyuki Ijima: "Animal Cell Technology:Basic & Applied Aspects Vol.4" Kluwer Academic Publishers, 584 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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