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Development of high performance hybrid artificial liver and its evaluation in preclinical test

Research Project

Project/Area Number 08555206
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
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 Masa-aki  Suzuki Shokan Co., LTD.・Tsukuba-Lab.Manager & Researcher, 筑波研究所, 所長代理(研究員)
SUGIMACHI Keizo  Kyushu Univ.・Dept.Surgery II・Prof., 医学部, 教授 (00038762)
IJIMA Hiroyuki  Kyushu Univ.・Dept.Chem.Eng.・Lecture, 工学部, 講師 (10274515)
MATSUSHITA Taku  Kyushu Univ.・Dept.Chem.Eng.・Assoc.Prof., 工学部, 助教授 (10209538)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 1997: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1996: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsHybrid artificial liver / Plasma of hepatic failure patient / Hepatocyte spheroid / Polyurethane foam / Multi-capillary PUF packed-bed / Extracorporeal circulation / lschemic liver failure dog / lschemic liver failure pig / ブタ肝細胞スフェロイド / 多細管PUF充填層 / 温虚血肝不全ブタモデル / 血中アンモニア / 双方向フロー型培養装置 / 肝不全 / 温虚血性イヌ肝不全モデル / 多細管型PUF充填層 / 血糖値
Research Abstract

1.We developed a perfusion culture system of porcine hepatocyte spheroids (module volume ; 18.8cm^3, cell weight ; 2g, total plasma volume ; 140ml), and evaluated the functions of the spheroids in plasma of hepatic failure patient. Porcine hepatocyte spheroids mainatained ammonia decreasing activity in human plasma at least 3 days of culture.
2.For a validation of the performance of our artificial liver using large animals, we made hybrid artificial liver module (multi-capillary polyurethane foam (PUF) packed-bed, vulume ; 380 cm ^3) containing 30 g of dog hepatocyte which corresponded about 10% of a dog liver weight. When the module was applied to ischemic liver failure dogs (body weight ; 15 kg), blood glucose concentration was maintained, increase of blood ammonia concentration was suppressed and so on by the artificial liver treatment. These performances were comparable or slightly superior than those of Demetriou's artificial liver which was already used clinically as a bridge use for liver transplantation.
3.As preclinical step, we developed an artificial liver module using porcine hepatocyte spheroids (volume ; 380 cm^3*2) containing 64 g of cells, and applied to ischemic liver failure pigs (body weight ; 25 kg). Consequently, we could succeed suppression of the increase of blood ammonia concentration and extension of survival time.
These results suggest that our hybrid artificial liver system is a promising equipment for recovery from hepatic failure condition in human medical care.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 船津 和守: "ハイブリッド型人工肝臓とバイオレオロジー" 日本バイオレオロジー学会誌. 10巻2号. 40-49 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Ijima: "Spheroid formation of primary dog hepatocytes using polyurethane foam and its application to hybrid artificial liver" Animal Cell Technology:From Vaccines to Genetic Medicine. 557-583 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Funatsu: "Development of drug metabolism simulator using three-dimensional culture of hepatocytes of rats and dogs" Animal Cell Technology:From Vaccines to Genetic Medicine. 85-90 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 琢: "PUF/肝細胞スフェロイド充填層型人工肝臓のイヌ温虚血肝不全モデルへの適用" 人工臓器. 26巻2号. 455-459 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Nakazawa: "Prolonged Lidocaine Metabolizing Activity of Primary Hepatocytes with Spheroid Culture Using Polyurethane Foam as a Culture Substratum" Cytotechnology. 24巻3号. 235-242 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 船津 和守: "ヒト臨床を目指したハイブリッド型人工肝臓補助システムの開発" 生体材料. 15巻6号. 240-247 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 井嶋 博之: "肝臓病学の最前線" 中外医学社, 6 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Hybird artificial liver and biorheology" J.Jpn.Soc.Biorheology. Vol.10. 40-49 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Ijima: "Spheroid formation of primary dog hepatocytes using polyurehane foam and its application to hybrid artificial liver" Animal Cell Technology : Form Vaccines to Genetic Medicine. 557-583 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Development of drug metabolism simulator using three-dimensional culture of hepatocytes of rats and dogs" Animal Cell Technology : Form Vaccines to Genetic Medicine. 85-90 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taku Matsushita: "Application of hybrid artificial liver using PUF/hepatocytes-spheroid packed-bed module to warm ischemic liver failure dog" Jpn.J.Artif.Organs. Vol.26. 455-459 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kohji Nakazawa: "Prolonged lidocaine metabolizing activity of primary hepatocytes with spheroid culture using polyurethane foam as a culture substratum" Cytotechnology. Vol.24. 235-242 (1197)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Development of hybrid artificial liver support system for human clinical care" J.Jpn.Soc.for Biomaterials. Vol.15. 240-247 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroyuki Ijima: Kanzobyogaku no saizensen 1997 (Japanese). Tyugai-igaku Inc.Co., 409 (345-350) (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松下 琢: "PUF/肝細胞スフェロイド充填層型人工肝臓のイヌ温虚血肝不全モデルへの適用" 人工臓器. 26巻2号. 455-459 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井嶋 博之: "PUF/肝細胞スフェロイド充填層型人工肝臓の薬物誘導肝不全ラットへの適用" 人工臓器. 26巻3号. 719-723 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Funatsu: "Finite Element Analysis of 3-dimensional Flow in Agitated Bioreactors" Animal Cell Technology. Vol.8. 75-82 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Nakazawa: "Prolonged Lidocaine Metabolizing Activity of Primary Hepatocytes with Spheroid Culture Using Polyurethane Foam as a Culture Substratum" Cytotechnology. 24巻3号. 235-242 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中澤 浩二: "ヒト臨床を目指したハイブリッド型人工肝臓体外循環システムの開発" 組織培養工学. 23巻8号. 301-306 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 船津 和守: "ヒト臨床を目指したハイブリッド型人工肝臓補助システムの開発" 生体材料. 15巻6号. 240-247 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井嶋 博之: "肝臓病学の最前線" 中外医学社, 6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 和田 茂久: "肝不全ラットを用いた体外循環によるPUF/肝細胞スフェロイド充填層型人工肝臓の開発" 人工臓器. 25巻3号. 678-682 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.FUNATSU: "Development of drug metabolism simulator using three-dimensional culture of hepatocytes of rats and dogs" Animal Cell Technology:From Vaccines to Genetic medicine. 85-90 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.IJIMA: "Spheroid formation of primary dog hepatocytes using polyurethane foam and its application to hybrid artificial liver" Animal Cell Technology:From Vaccines to Genetic medicine. 557-583 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 船津 和守: "ハイブリッド型人工肝臓とバイオレオロジー" 日本バイオレオロジー学会誌. 10巻2号. 40-49 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 船津 和守: "ハイブリッド型人工肝臓" バイオサイエンスとインダストリー. 55巻1号. 21-24 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.NAKAZAWA: "Prolonged lidocaine metabolizing activity of primary hepatocytes with spheroid culture using polyurethane foam as a culture substratum" Cytotechnology. (in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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