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Development of an hybrid artificial liver for human medical use equipped with the newest regulation system for control of culture environment of hepatocytes

Research Project

Project/Area Number 06555248
Research Category

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

Allocation TypeSingle-year Grants
Research Field 生物・生体工学
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) ABE Masaaki  Suzuki Shokan Co., LTD.・Tsukuba-Lad.・Manager & Researcher, 所長代理(研究員)
MATSUSHITA Taku  Kyushu Univ.・Dept.Chem.Eng.・Assoc.Prof., 工学部, 助教授 (10209538)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1994: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsHybrid artificial liver / Hepatic failure / Hepatocyte spheroid / Bi-directional flow system / Ischemic liver failure dog / Multi-capillary PUF packed-bed / Blood glucose level / Ketone body ratio / ガス圧送送液システム / 双方向フローシステム / 多細管型ポリウレタンフォーム充填層 / スフェロイド / 酸素消費速度 / 体外循環システム
Research Abstract

1. We developed a prototype module (multi-capillary PUF packed-bed) of hybrid artificial liver for recovery of hepatic failure dogs, which was required for an evaluation of the performance of this module using PUF/spheroid packed-bed for human medical use. Last year, we could succeed in recovery of a hepatic failure rat treated by 5cm^3 of module containing about 5*10^7 cells which corresponded to about 10% of liver cells. In the case of dog, we designed about 300cm^3 of module containing 3*10^9 cells (30g of cells) which corresponded to about 10% of dog liver cells. The diameter and the pitch of a capillary were 2mm and 4mm, respectively.
2. Opimum flow rate of medium/plasma related to reveal the maximum performance of the hybrid artificial liver module was calculated to be 400 ml/min from the results of small scale experiment using rat. Dissolved oxygen concentration (DO) gradient occurred in the module seemed to be avoided by bi-directional flow of medium inside of the module. The performance which indicated by albumin secretion rate of hepatocytes immobilized in the module under pH ; 7.2 and DO ; 6.5 of controlled culture condition, was comparable with static culture of hepatocytes. These results indicated that the scale up of module was successful.
3. We applied this artificial liver module to acute ischemic liver failure dogs for evaluation of practicality of the module for human medical care, and investigated the change of some biochemical components in blood as index of liver function. Consequently, we could succeed in the maintenance blood glucose level and ketone body ratio, and suppress the increase of blood ammonia and bilirubin levels. These results suggest that the artificial liver module is a promising equipment for recovery of hepatic failure condition in medical use.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] 松下 琢: "肝不全ラット体外循環によるポリウレタンフォーム(PUF)/肝細胞スフェロイド充填層型人工肝臓の性能評価" 人工臓器. 24. 815-820 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Matsushita: "Development of a hybrid arificial liver support system using PUF/spheroid packed-bed" Animal Cell Technology. 7. 1049-1053 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 松下 琢: "ハイブリッド型人工肝臓補助システム" 組織培養. 21. 21-24 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 船津和守: "バイオエンジニアリングの歴史-BEは社会にどのような貢献をしてきたか-人工肝臓開発の流れと今後の展望" バイオエンジニアリング報. 19. 1-4 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 中澤浩二: "Development of Drug metabolism simulator for alternatives to animal experimentation using 3-demensional culture of hepatocytes" Proceedings of the 9th Annual Meeting of the Japanese Society for Alternatives to Animal Experiments. 9. 114-115 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 船津和守: "ハイブリッド型人工肝臓プロトタイプの開発と小動物実験による実用性の評価" 日本機械学会第73期全国大会講演論文集. 4. 21-23 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 船津和守: "メディカルテクノロジーへの招待" 株式会社 培風館, 20 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 船津和守: "新タンパク質応用工学" 株式会社 フジ・テクノシステム, 5 (527-532) (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taku Matsushita: "Estimation of the performance of a PUF/spheroid packed-bed type artificial liver by using an extracorporeal circulation with hepatic failure rats" Jpn.J.Artif.Organs. Vol.24. 815-820 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taku Matsushita: "Development of a hybrid artificial liver support system using PUF/spheroid packed-bed" Animal Cell Technology. Vol.7. 1049-1053 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taku Matsushita: "Hybrid artificial liver support system" The Tissue Culture. Vol.21. 473-476 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "The History of Bioengineering -The stream of development of hybrid artificial liver support system-" Bioengineering Report. Vol.19. 1-4 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kohji Nakazawa: "Development of drug metabolism simulator for alternatives to animal experimentation using 3-dimensional culture of hepatocytes" Proc.of the 9th Ann.Meeting of Jpn.Soc.for Alternatives to animal Experiments. Vol.9. 114-115 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Development of a proto-type hybrid artificial liver and evaluation of the practicality of the artificial liver by using hepatic failure small animals" Proc.of the 73rd Ann.Meeting of Jpn.Soc.Mech.Eng.Vol.4. 21-23 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazumori Funatsu: Introduction for Medical Technology. Baifukan Inc.Co., 143 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kazumori Funatsu: New Applied Protein Engineering. Fuji Techno System Inc.Co., 950 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 松下 琢: "肝不全ラット体外循環によるポリウレタンフォーム(PUF)/肝細胞スフェロイド充填層型人工肝臓の性能評価" 人工臓器. 24. 815-820 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] T.Matsushita: "Development of a hybrid artificial liver support system using PUF/spheroid packed-bed" Animal Cell Technology. 7. 1049-1053 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 松下 琢: "ハイブリッド型人工肝臓補助システム" 組織培養. 21. 21-24 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 船津和守: "バイオエンジニアリングの歴史-BEは社会にどのような貢献をしてきたか-人工肝臓開発の流れと今後の展望" バイオエンジニアリング報. 19. 1-4 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 中澤 浩二: "Development of drug metabolism simulator for alternatives to animal experimentation using 3-dimensional culture of hepatocytes" Proceedings of the 9th Annual Meeting of the Japanese Society for Alternatives to Animal Experiments. 9. 114-115 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 船津和守: "ハイブリッド型人工肝臓プロトタイプの開発と小動物実験による実用性の評価" 日本機械学会第73期全国大会講演論文集. 4. 21-23 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 船津和守: "メディカルテクノロジーへの招待" 株式会社 培風館, 20 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 船津和守: "新タンパク質応用工学" 株式会社 フジ・テクノシステム, 5(527-532) (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Funatsu: "High density culture of animal cells and its application to hybrid artificial liver support systems in Japan" Artificial Organs Today. 4. 253-274 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 井嶋博之: "多細管型PUF/スフェロイド充填層を用いたハイブリッド型人工肝臓の開発" 人工臓器. 23. 463-468 (1994)

    • Related Report
      1994 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. 469-472 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Ijima: "Establishment of a rat extracorporeal circulation system to estimate the performance of a hybrid artificial liver" Animal Cell Technology:Basic & Applied Aspects. 6. 395-399 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Funatsu: "Application of three dimensional culture of adult rat hepatocytes in polyurethane foam pores for an artificial liver support system" Proccedings of '94 Annual Meeting of KSAP & The 3rd symposium on new drug development. 137-144 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 船津和守: "ハイブリッド型人工肝臓の開発" ケミカルエンジニアリング. 39. 29-34 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] T.Matsushita: "Better Living Through Innovative Biochemical Engineering" Continental Press Pte Ltd, 880 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 松下琢: "バイオプロセスシステム工学" 株式会社 アイピーシー, 687 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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