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Basic Study for Regenerative Medicine : Differentiate of Embryonic Stem Cells to Hepatocytes and Expressions of Cytochrome P450 in the Differentiating Cells

Research Project

Project/Area Number 15390047
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionShinshu University

Principal Investigator

OHMORI Shigeru  Shinshu University, Shinshu University Hospital, Division of Pharmacy, Professor, 医学部附属病院, 教授 (70169069)

Co-Investigator(Kenkyū-buntansha) MATSUNAGA Tamihide  Shinshu University, Shinshu University Hospital, Division of Pharmacy, Associate Professor, 医学部附属病院, 助教授 (40209581)
SASAKI Katsunori  Shinshu University, Shinshu University School of Medicine, Department of Anatomy and Organ Technology, 医学部, 教授 (30170666)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥9,400,000 (Direct Cost: ¥9,400,000)
Keywordsmouse / monkey / embryonic stem cell / hepatocyte / differentiate / hepatoblast / cyochrome P450 / CYP3A / CYP3A8 / CYP3A66 / HNF-3β / 胚様体 / 薬物トランスポーター / Cyplal / Cyp3all / Cyp7al / Cyp7bl
Research Abstract

To differentiate mouse embryonic stem (ES) cells to hepatocytes, embryoid bodies were cultured for 36 days. Hepatocyte differentiation markers were expressed in the cells differentiated from ES cells. The expression pattern of cytochrome P450 (CYP) genes in the cells could be grouped into four different categories, such as highly expressed at early to mid stage, only expressed at late stage ; expressed throughout at all stages and not detectable at any stages. Aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator and glucocorticoid receptor were detected in the cells cultured throughout the time course. Pregnane X receptor was detected only the cells cultured for more than 24 days. The alpha-fetoprotein and albumin were co-expressed with CYP3A2 and CYP1A1, respectively. Monkey ES cells were also differentiated into hepatocytes in vitro. The cells expressed alpha-fetoprotein, albumin, CYP3A8, CYP3A66 and CYP7A1. We have isolated a cDNA clone from the differentiating monkey ES cells and identified a novel CYP isoform, named CYP3A7m. Deduced amino acid sequence of CYP3A7m shows 89, 81, 91 and 72% homology to CYP3A4, CYP3A5, CYP3A7 and CYP3A43, respectively. These results suggested that CYP and transcription factor genes were expressed in hepatocytes differentiated from ES cells and those expression levels and patterns were considerably changed in individual enzymes during the course of the differentiation.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (10 results)

All 2006 2005 2004

All Journal Article (10 results)

  • [Journal Article] Determination of P-glycoprotein ATPase activity using luciferase.2006

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Biol Pharm Bull 29

      Pages: 560-564

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Effective NADH-Dependent Oxidation of 7β-Hydroxy-Δ^8-tetrahydrocannabinol to the Corresponding Ketone by Japanese Monkey Hepatic Microsomes2005

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Biol Pharm Bull 28

      Pages: 646-651

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Characterization of Human Fetal Hepatocytes : Expression and Induction of CYP3As2005

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Proceedings of the 15^<th> Intl. Symposium on MDO

      Pages: 99-102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Induction mechanisms of CYP3As in human fetal hepatocytes by glucocorticoids.2005

    • Author(s)
      Maruyama M et al.
    • Journal Title

      Drug Metab Rev 37

      Pages: 147-147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Simple and highly sensitive method for determination of P-glycoprotein ATPase activity using Luciferase.2005

    • Author(s)
      Ohmori S et al.
    • Journal Title

      Drug Metab Rev 37

      Pages: 176-176

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Expressions of cytochrome P450 in differentiating mouse embryonic stem cells.2005

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Drug Metab Rev 37

      Pages: 200-200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Effective NADH-Dependent Oxidation of 7β-Hydroxy-Δ^8-tetrahydrocannabinol to the Corresponding Ketone by Japanese Monkey Hepatic Microsomes.2005

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Biol Pharm Bull 28

      Pages: 646-651

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of Human Fetal Hepatocytes : Expression and Induction of CYP3As2005

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Proceedings of the 15^<th> Intl.Symposium on MDO (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expression and induction of CYP3As in human fetal hepatocytes.2004

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Biochem Biophys Res Commun 318

      Pages: 428-434

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Characterization of Human Fetal Hepatocytes : Expression and Induction of CYP3As.2004

    • Author(s)
      Matsunaga T et al.
    • Journal Title

      Proceedings of the 15^<th> Intl.Symposium on MDO, Medimonde S.r.l., Bologna, Itary

      Pages: 99-102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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