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Development of the hepatic toxicity evaluation test using a mini-bioartificial liver and ^<13>C stability isotope compounds

Research Project

Project/Area Number 17590476
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionJIKEI UNIVERSITY

Principal Investigator

MATSUURA Tomokazu  Jikei University, School of Medicine, Lecturer, 医学部, 講師 (30199749)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordstoxic evaluation test / bioartificial organ / substitute organ / stability isotope / breath test / glucose metabolism / cancer / 3 dimensional cell culture / バイオ人工肝臓 / ^<13>C
Research Abstract

The xinobiotic evaluation method used by human cells is a technique to fill metabolic differences between Homo sapiens and experimental animals. However, conventional single-layered culture method cannot reproduce the functions of cell in the body. We can use the bioartificial organs which we made by three-dimensional high density culture method as a substitute organ of human tissue and organs. In the present study, we performed development of the metabolic and toxic test using ^<13>C stability isotope compounds for sensitive metabolic evaluation in a substitute organ.
Three-dimensional culture in a bioreactor is a large-scaled culture compared to single-layered culture. Therefore it is difficult to operate a lot of reactors. On this account a system to carefully judge the operation situation of one reactor is necessary. At first we made a mixed gas feeder to maintain simply three-dimensional culture system, without a CO_2 incubator and a large-scaled controller, supplied oxygen of cult … More ure system. I also developed the metabolism discharge ^<13>CO_2 assay method using a ^<13>C stability isotope labeled compound to perform toxic evaluation and a certain specific metabolism evaluation on culture course. The advantages of this method are ; 1)We can evaluate a specific metabolism by using a specific labeled compound, 2)We can easily get samples as exhaust gas from a reservoir, and do not need to open a reactor, and 3) We can easily measure ^<13>CO_2 for only 2'30" by a infrared spectrophotometer.
As a result of this study, we developed the metabolic and toxic evaluation system for performing metabolic simulation in the body using bioartificial organs and ^<13>C stability isotope labeled compounds. Objective evaluation will apply metabolism modeling and computer simulation. Before animal and clinical examinations, the substitute analysis using bioartificial organs and a stability isotope labeled compounds will become useful for evaluation of the toxicity/metabolism of quality of drugs and foods in future. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006 2005

All Journal Article (22 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] A comprehensive gene expression analysis of human hepatocellular carcinoma cell lines as components of bioartificial liver using radial flow bioreactor.2007

    • Author(s)
      Kosuge M, Takizawa M, Maehashi H, Matsuura T, Matsufuji S
    • Journal Title

      Liver Int. 27

      Pages: 101-108

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] An extracorporeal bioartificial liver in treatment of pigs with experimental hepatic encephalopathy.2007

    • Author(s)
      Kanai H, Marushima H, Kimura F, Iwaki T, Ohkawa K, Yanaga K, Matsuura T, et al.
    • Journal Title

      Artificial Organs 31

      Pages: 148-151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The hepatic sinusoidal endothelial lining and colorectal liver metastasis2007

    • Author(s)
      Braet F, Nagatsuma K, Saito M, Soon L, Wisse E, Matsuura T
    • Journal Title

      World J Gastroenterol 13(6)

      Pages: 821-825

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] An extracorporeal bioartificial liver in treatment of pigs with experimental hepatic encephalopathy.2007

    • Author(s)
      Kanai H, Marushima H, Kimura F, Iwaki T, Ohkawa K, Yanaga K, Matsuura T., et al.
    • Journal Title

      Artificial Organs 31

      Pages: 148-151

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The hepatic sinusoidal endothelial lining and colorectal liver metastasis.2007

    • Author(s)
      Braet F, Nagatsuma K, Saito M, Soon L, Wisse E, Matsuura T
    • Journal Title

      World J Gastroenterol 13(6)

      Pages: 821-825

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] An extracorporeal bioartificial liver in treatment of pigs with experimental hepatic encephalopathy.2007

    • Author(s)
      Kanai H, Marushima H, Kimura F, Iwaki T, Ohkawa K, Yanaga K, Matsuura T et al.
    • Journal Title

      Artificial Organs 31

      Pages: 148-151

    • Related Report
      2006 Annual Research Report
  • [Journal Article] All-trans retinoic acid down-regulates human albumin gene expression through the induction of C/EBP beta-LIP2006

    • Author(s)
      Masaki T, Matsuura T, Ohkawa K, Miyamura T, Okazaki I, Watanabe T, Suzuki T
    • Journal Title

      Biochem J 397

      Pages: 345-353

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Reconstruction of liver organoid using a bioreactor2006

    • Author(s)
      Saito M, Matsuura T, Masaki T, Maehashi H, Shimizu K, Hataba Y, Iwahori T, Suzuki T, Braet F
    • Journal Title

      World J Gastroenterol 12

      Pages: 1881-1888

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] hree-dimensional cell culture of hepatocytes using apatite-fiber scafford and application to a radial-flow bioreactor2006

    • Author(s)
      Hiramoto A, Matsuura T, Aizawa M
    • Journal Title

      Archiv BioCeramics Res 6

      Pages: 220-223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Bioreactors for 3-dimensional high-density culture of human cells2006

    • Author(s)
      Matsuura T
    • Journal Title

      Human Cell 19

      Pages: 11-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] ハイブリッド人工肝臓・体外循環型バイオ人工肝臓の開発と臨床応用への問題点2006

    • Author(s)
      松浦知和, 岩城隆昌, 木村直史, 石井雄二, 矢永勝彦
    • Journal Title

      再生医療 5

      Pages: 395-400

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] All-trans retinoic acid down-regulates human albumin gene expression through the induction of C/EBP beta-LIP.2006

    • Author(s)
      Masaki T, Matsuura T, Ohkawa K, Miyamura T, Okazaki I, Watanabe T, Suzuki T
    • Journal Title

      Biochem J 397

      Pages: 345-353

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reconstruction of liver organoid using a bioreactor.2006

    • Author(s)
      Saito M, Matsuura T, Masaki T, Maehashi H, Shimizu K, Hataba Y, Iwahori T, Suzuki T, Braet F
    • Journal Title

      World J Gastroenterol 12

      Pages: 1881-1888

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Three-dimensional cell culture of hepatocytes using apatite-fiber scafford and application to a radial-flow bioreactor.2006

    • Author(s)
      Hiramoto A, Matsuura T, Aizawa M
    • Journal Title

      Archiv Bio Ceramics Res. 6

      Pages: 220-223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bioreactors for 3-dimensional high-density culture of human cells.2006

    • Author(s)
      Matsuura T
    • Journal Title

      Human Cell 19

      Pages: 11-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reconstruction of liver prganoid using a bioreactor2006

    • Author(s)
      Saito M, Matsuura T, Masaki T, Maehashi H, Shimizu K, Hatabe Y, Iwahori T, Braet F
    • Journal Title

      World J Gastroenterol 12

      Pages: 1881-1888

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reconstruction of Liver organoid Using a Bioreactor2006

    • Author(s)
      Saito M, Matsuura T, Masaki M, Maehashi H, Shimizu K, Hatabe Y, Iwahori T, Suzuki T, Bract F
    • Journal Title

      World J Gastroentorol 12(12)

      Pages: 1881-1888

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bioreactors for 3-dimensional high density culture of human cells2006

    • Author(s)
      Mtsuura T
    • Journal Title

      Human Cell (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Two-dimensional protein analysis of functional liver cells for bioartificial liver2005

    • Author(s)
      Hascilowicz T, Kosuge M, Matsuura T, Matsufuji S, Murai N
    • Journal Title

      Jikeikai Med. J. 52(4)

      Pages: 109-114

    • NAID

      10024471931

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 再生医療を支えるセラミックス・多孔質水酸アパタイトを用いたバイオ人工肝臓2005

    • Author(s)
      松浦知和, 幡場良明, 石川周太郎, 小川哲朗
    • Journal Title

      セラミックス 40

      Pages: 869-872

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Two-dimensional protein analysis of functional liver cells for bioartificial liver.2005

    • Author(s)
      Hascilowicz T, Kosuge M, Matsuura T, Matsufuji S, Murai N
    • Journal Title

      Jikeikai Med.J. 52(4)

      Pages: 109-114

    • NAID

      10024471931

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 多孔質水酸アパタイトを用いたバイオ人工肝臓2005

    • Author(s)
      松浦知和, 幡塲良明, 石川周太郎, 小川哲朗
    • Journal Title

      セラミックス 40

      Pages: 869-872

    • NAID

      10018278237

    • Related Report
      2005 Annual Research Report
  • [Book] 図説 クリニカルサインと臨床検査.(中野昭一編)2005

    • Author(s)
      松浦知和
    • Total Pages
      421
    • Publisher
      医歯薬出版(株)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ガス混合装置及びガス混合法2006

    • Inventor(s)
      藤原邦彦, 松浦知和
    • Industrial Property Rights Holder
      エイブル(株), 大川 清, 松浦知和
    • Industrial Property Number
      2006-050548
    • Filing Date
      2006-02-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ガス混合装置及びガス混合法2006

    • Inventor(s)
      藤原邦彦, 松浦知和
    • Filing Date
      2006-02-27
    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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