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Engineering research on the production of useful biologicals by mass culture of animal and plant cells

Research Project

Project/Area Number 02453113
Research Category

Grant-in-Aid for General 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) KAJIWARA Toshihisa  Kyushu Univ.・Dept.Chem.Eng.・Assoc.Prof., 工学部, 助教授 (10194747)
MATSUSHITA Taku  Kyushu Univ.・Dept.Chem.Eng.・Res.Assis., 工学部, 助手 (10209538)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1990: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsAnimal Cell / Plant Cell / High Density Mass Culture / beta-Carotene / Air-Lift Vessel / Hybrid Artificial Liver / PID Regulation / Three-Dimensional Flow Simulation / βーカロチン / 血栓溶解酵素 / 発泡ポリウレタン充填層 / エア-リフト槽 / ポリウレタンフォ-ム / バイオリアクタ- / ドラフトチュ-ブ付エア-リフト槽
Research Abstract

1. We could succeed in regulating a dissolved oxygen concentration (DO) of the medium in PID manner by using DO electrode, DO converter, PID controller and mass flow controller, in which the gas flow rate was used as the manipulated variable. By using the DO control system, it was found that there were optimum DO level in cell growth (3.0ppm) and beta-carotene production (0.05ppm) of carrot cells in an air-lift column with draft tube. Highest productivity (0.24mug/10^8cells/day) was obtained in DO-stat (0.15ppm) semi-continuous culture of carrot cells and this value was 7.5 time higher than that in the usual batch culture. We also succeeded in high density culture (1.1X10^8cells/cm^3) of animal cells by regulating a out-put DO level (more than 5.8ppm) of polyurethane foam (PUF) packed-bed culture system.
2. The three-dimensional laminar flow of culture medium in an agitated vessel with 2-bladed paddle imoeller was simulated numerically by finite element method. The Carreau model was used as the constitutive equation. We succeeded in obtaining the fields of the velocity and the shear stress under a certain agitation rate (10-60 rpm).
3. Adult rat hepatocytes formed spherical multicellular aggregates (spheroids, about 100mum in diameter) when they were cultured in the pores of PUF. Highly differentiated hepatic functions were maintained in the spheroid, These spheroids were partly attached and immobilized in the pores of PUF. We designed a PUF/spheroid packed-bed culture system. Albumin and urea production activities of hepatocyte/spheroid immobilized in the PUF packed-bed were higher than those of usual hepatocyte/monolayer culture in petri dish, and these activities were maintained for 26 days. These results indicated that the PUF/spheroid packed-bed culture system provided a promising prototype of hybrid type artificial liver support system.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [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" 化学工業. 56. 385-386 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Hybrid Artificial Liver Undergoing Testing" Medical Equipmint Journal of Japan. 36. 10 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 船津 和守: "肝細胞培養装置-人工肝臓の開発を目指して-" 遺伝. 47. 85-90 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taku Matsushita: "BIOCHEMICAL ENGINEERING FOR 2001" Springer-Verlag, 847 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroyuki Ijima: "Animal Cell Technology:Basic & Applied Aspects Vol.4" Kluwer Academic Publishers, 584 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taku Matsushita: "A study on method for high density culture of anchorage-dependent mammalian cells" Kagaku Kougaku. 56. 385-386 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Hybrid artificial liver under-going testing" Medical Equipment J. of Japan. 36. 10 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taku Matsushita: "Development of a hybrid type artificial liver utilizing three dimensional culture of adult hepatocytes" Jpn. J. Artif. Organs. 21. 1050-1054 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kazumori Funatsu: "Culture vessel of hepatocytes" The Heredity. 47. 85-90 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Taku Matsushita: "Application of three dimensional culture of adult rat hepatocytes in PUF pores for artificial liver support system" Springer-Verlag, Biochemical Engineering for 2001. 339-342 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hiroyuki Ijima: "Application of three dimensional culture of adult rat hepatocytes in PUF pores for artificial liver support system" Kluwer Academic Publishers Animal Cell Technology : Basic & Applied Aspects. Vol.4. 81-86 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [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] 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] 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] Taku Matsushita: "BIOCHEMICAL ENGINEERING FOR 2001" Springerー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
  • [Publications] Taku Matsushita: "High albumin production by multicellular spheroids of adult rat hepatocytes formed in the pores of polyure thane foam" Applied Microbiology and Biotechnology. 36. 324-326 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Taku Matsushita: "High density culture of anchorageーdependent mammalian cells for production of useful biologicals in polyurethane foam packedーbed culture systems" Memoirs of the Faculty of Engineering Kyushu University. 51. 313-328 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Taku Matsushita: "High density culture of ancorageーdependent animal cells by polyurethane foam packedーbed culture systems" Applied Microbiology and Biotechnology. 35. 159-164 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松下 琢: "ドラフトチュ-ブ付きエア-リフト槽によるニンジン細胞の高密度培養" 化学工学論文集. 17. 649-654 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 川久保 康彦: "ポリウレタンフォ-ムを付着担体とした弱付着性ヒト腎細胞の高密度培養による血栓溶解酵素の生産" 化学工学シンポジウムシリ-ズ「生物機能の応用とバイオリアクタ-」. 25. 174-179 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松下 琢: "初代肝細胞のPUF三次元培養によるハイブリッド型人工肝臓の開発" 化学工学. 55. 868-870 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 船津 和守(分担): "新しい食品加工技術と装置(細胞大量培養)" (株)産業調査会事典出版センタ-, 1161 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 小川 勝也: "ニンジン培養細胞からの高純度βーカロチンの簡便な精製法の確立" 化学工学論文集. 17. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Taku Matsushita: "High density culture of anchorageーdependent animal cells by polyurethane foam packedーbed culture systems" Applied Microbiology and Biotechnology. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 松下 琢: "ドラフトチュ-ブ付きエア-リフト槽によるニンジン細胞の高密度培養" 化学工学論文集. 17. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Taku Matsushita: "High albumin production by multicellular spheroids of adult rat hepatocytes formed in the pores of poly urethane foam" Applied Microbiology and Biotechnology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Taku Matsushita: "Development of waste metabolites removal system in animal cell culture" Cytotechnology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Yasuhiko Kawakubo: "TーPA production by high density culture of human kidney cells in polyurethane foam packedーbed culture system" Biotechnology and Bioengineering.

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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