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Research system of toxicity for human liver cell lines

Research Project

Project/Area Number 08557033
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Public health/Health science
Research InstitutionJikei University School of Medicine

Principal Investigator

SHIMIZU Hidesuke  Jikei University School of Medicine, Professor, 医学部, 教授 (80056879)

Co-Investigator(Kenkyū-buntansha) MATSUURA Tomokazu  Jikei University School of Medicine, Assistant, 医学部, 助手 (30199749)
SUZUKI Pul.Yuji  Jikei University School of Medicine Assistant Professor, 医学部, 講師 (30163017)
HASUMURA Satoshi  Jikei University School of Medicine, Assistant Professor, 医学部, 講師 (30189518)
NAGAMORI Seishi  Jikei University School of Medicine, Associate Professor, 医学部, 助教授 (60119831)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1997: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1996: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsradial flow bioreactor / human liver cancer cell / mutagens / metabolism of toxicity / 環境汚染物質 / 変異原性 / ヒト由来肝細胞 / ラジアルフロー / バイオリアクター / 薬物代謝 / 実験動物 / 細胞障害
Research Abstract

Cell morphology and function for a newly developed hepatocytes culture system cmploying highly functional human liver cell line, FLC,cultured in a radial flow bioreactor were compared to cells grown in a conventional monolayr culture. The radial flow bioreactor consists of a vertically-extended cylindrical matrix comprised of porous glass bead microcarriers through which liquid medium flows from the periphery in toward the central axis generating a beneficial concentration gradient of exygen and nutrients while preventing excessive shear stresses or build up of waste products. The three dimensional culture system supports high-density and long-term viability. Scanning and transmission electron microscopy revealed that cells cultured in a monolayr system were flattened and extended with numerous cytoplasmic projections. Cells in the three-dimensional culture were spherical and covered with microvilli-like processes resembling liver cells in vivo. The cells were solidly attached on the surfaces and within the pores of the microcarriers in highly dense colonies. FLC cells metabolized antipyrine, nafamostat mesilate, and ammonia. This indicated that FLC cells were equiped with activities of cytochrome P450, carboxylesterase and urea cycle. Micronucleus research proved that FLC cells were available for investigation of mutagens. Results demonstrated that FLC cells in a radial flow bioreactor system provides a superior three-dimensional culture environment which allows cells to metabolize toxicities and this system had the ability to be an artificial liver to investigate human liver metabolism of toxicity.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 永森 静志: "人工肝臓の開発" 組織培養工学. 23巻. 280-283 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 蓮村 哲: "ヒト由来肝癌細胞を用いたラジアルフロー型バイオリアクターによるアルブミン大量産生" 人工血液. 5巻. 33-37 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 松浦 知和: "人工肝に利用する細胞-肝実質細胞と非実質細胞-" 組織培養工学. 23巻. 288-291 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tomokazu Matsuura: "High density culture of immortalized liver endothelial cells in the radial-flow bioreactor for development of an artificial liver" Int.J.Artif.Organs. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masaaki Kawada: "Massive Culture of Human Liver Cancer Cells in a Newly Developed Radial Flow Bioreactor System : Ultrafine Structure of Functionally-Enhanced Hepatocarcinoma Cell Lines." In Vitro Cellular & Developmental Biology. 34. in press (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 川田 雅昭: "新しい長期三次元高密度大量培養法による人工肝補助装置-ラジアルフロー型バイオリアクターの機能評価-" 肝臓. 38巻. 70-71 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Masaaki Kawada: "Massive Culture of Human Liver Cancer Cells in a Newly Developed Radial Folw Broreactor System : Ultrafine Structure of Functionally-Enhanced Hepatocarcinoma Cell Lines. (in press)" In Vitro Cellular & Developmental Biology. Vol.34 No.2. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tomokau Matsuura: "High density culture of immortalized liver endothelial cells in the radial-flow bioreactor for development of an artificial liver." Int.J.Artif.Organs. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 永森静志: "人工肝臓の開発" 組織培養工学. 23巻8号. 280-283 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 蓮村 哲: "ヒト由来肝癌細胞を用いたラジアルフロー型バイオリアクターによるアルブミン大量産生" 人工血液. 5巻3号. 33-37 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 松浦知和: "人工肝に利用する細胞-肝実質細胞と非実質細胞-" 組織培養工学. 23巻8号. 288-291 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 川田雅昭: "新しい長期三次元高密度大量培養法による人工肝補助装置-ラジアルフロー型バイオリアクターの機能評価-" 肝臓. 38巻4号. 70-71 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 川田雅昭: "肝臓の代謝検定利用-In Vitroに代わって-" 組織培養工学. 23巻8号. 307-309 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagamori,S: "A new Liver Support System Using A Radial Flow Bioreactor Proceeding of International congress in Hepatocytes-Application" Toxicology and Medicine. -54 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 永森静志: "バイオ人工肝補助装置のマイクロ化の開発" 医用マイクロマシン技術開発研究(厚生省科学研究費補助金医用マイクロマシン技術開発研究事業研究報告書. 183-196 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 永森静志: "医学ジャーナル" 薬剤による肝障害、新薬剤副作用軽減化の工夫, 12-27 (1995)

    • Related Report
      1996 Annual Research Report

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

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