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2012 Fiscal Year Final Research Report

Differentiation ofhuman iPS cells into hepatocytes and bile duct epithelial cells and application to drug development study

Research Project

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Project/Area Number 22390028
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  信州大学, 医学部附属病院, 教授 (70169069)

Co-Investigator(Kenkyū-buntansha) MATSUNAGA Tamihide  名古屋市立大学, 薬学研究科, 教授 (40209581)
NAKAMURA Katsunori  名古屋市立大学, 薬学研究科, 准教授 (20361363)
YAMAORI Satoshi  信州大学, 医学部附属病院, 准教授 (40360218)
Project Period (FY) 2010 – 2012
Keywords薬物動態 / 代謝学
Research Abstract

Human hepatocytes are useful for pharmacokinetic examinations. However, considerable donor-dependent variations are problematic. The small intestine, as well as liver, plays an important role in all aspects of pharmacokinetics. At present, human intestinal epithelial cells are difficult to obtain, and there is no appreciate model cells. Instead, other tissue cell-derived cell lines, including Caco-2 cells and MDCK cells, were used as intestinal model in a drug absorption study. Human iPS cells apparently differentiate into various types of mature cells, and are thereby an attractive source for routine access to large numbers of cells that can be used for the pharmacokinetic examinations replacing primary cells. In this study, we investigated the effects of small-molecule compounds for differentiation of human iPS cells into hepatocytes and enterocytes available in pharmacokinetic study.

  • Research Products

    (21 results)

All 2013 2012 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (13 results)

  • [Journal Article] Hepatocyte nuclear factor 6 activates the transcription of CYP3A4 in hepatocyte-like cells differentiated from human induced pluripotent stem cells2013

    • Author(s)
      Sasaki T, Takahashi S, Numata Y, Narita M, Tanaka Y, Kondo Y, Matsunaga T, Ohmori S, Nagata K
    • Journal Title

      Drug Metab. Pharmacokinet.

    • DOI

      DOI:;10.2133/dmpk.DMPK-12-RG-132

    • Peer Reviewed
  • [Journal Article] Clinical evidence of the pharmacokinetics change in thalidomide therapy2013

    • Author(s)
      Nakamura K, Matsuzawa N, Ohmori S, Ando Y, Yamazaki H, Matsunaga T
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 28 Pages: 38-43

    • DOI

      DOI:;10.2133/dmpk.DMPK-12-RV-089

    • Peer Reviewed
  • [Journal Article] Differentiation of monkey embryonic stem cells to hepatocytes by feeder-free dispersion culture and expression analyses of cytochrome P450 enzymes responsible for drug metabolism.2013

    • Author(s)
      Maruyama J, Matsunaga T, Yamaori S, Sakamoto S, Kamada N, Nakamura K, Kikuchi S, Ohmori S
    • Journal Title

      Biol Pharm Bull

      Volume: 36 Pages: 292-298

    • DOI

      DOI:;10.1248/bpb.b12-00866.

    • Peer Reviewed
  • [Journal Article] Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers.2012

    • Author(s)
      Tsuchiya H, Matsunaga T, Aikawa K, Kamada N, Nakamura K, Ichikawa H, Sasaki K, Ohmori S
    • Journal Title

      Drug Metabol. Pharmacokinet

      Volume: 27 Pages: 598-604

    • DOI

      DOI:;10.2133/dmpk.DMPK-12-RG-017.

    • Peer Reviewed
  • [Journal Article] Mechanisms of CYP3A induction by glucocorticoids in human fetal liver cells.2012

    • Author(s)
      Matsunaga T, Maruyama M, Matsubara T, Nagata K, Yamazoe Y, Ohmori S
    • Journal Title

      Drug Metabol Pharmacokinet

      Volume: 27 Pages: 653-657

    • DOI

      DOI:;10.2133/dmpk.DMPK-12-NT-018.

    • Peer Reviewed
  • [Journal Article] Lower expression of HNF4α and PGC1α might impair rifampicin-mediated CYP3A4 induction under conditions where PXR overexpressed in human fetal liver cells.2012

    • Author(s)
      Takezawa T, Matsunaga T, Aikawa K, Nakamura K, Ohmori S
    • Journal Title

      Drug Metabol Pharmacokinet

      Volume: 27 Pages: 430-438

    • DOI

      DOI:;10.2133/dmpk.DMPK-12-RG-126

    • Peer Reviewed
  • [Journal Article] Effects of hypoxia-inducible factor-1α chemical stabilizer, CoCl_2 and hypoxia on gene expression of CYP3As in human fetal liver cells.2012

    • Author(s)
      Suzuki E, Matsunaga T, Aonuma A, Sasaki T, Nagata K, Ohmori S
    • Journal Title

      Drug Metabol Pharmacokinet

      Volume: 27 Pages: 398-404

    • DOI

      DOI:;10.2133/dmpk.DMPK-12-RG-074.

    • Peer Reviewed
  • [Journal Article] CYP3As gene expression and testosterone 6β-hydroxylase activity in human fetal membranes and placenta at full term2010

    • Author(s)
      Maezawa K, Matsunaga T, Takezawa T, Kanai M, Ohira S, Ohmori S
    • Journal Title

      Biol Pharm Bull

      Volume: 33 Pages: 249-254

    • DOI

      DOI:;10.1248/bpb.33.249.

    • Peer Reviewed
  • [Presentation] ヒト iPS 細胞由来肝細胞の剥離・凍結保存法の検討2012

    • Author(s)
      三森佳代,近藤祐樹,吉橋幸美,荻原留理,岩尾岳洋,松永民秀
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      20121211-14
  • [Presentation] ヒト人工多能性幹細胞の肝細胞への分化における変法 L-15 培地及び血清の効果2012

    • Author(s)
      吉橋幸美,近藤祐樹,三森佳代,杉山留理,岩尾岳洋,金濱吉範,牧与志幸,松永民秀
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Year and Date
      20121211-14
  • [Presentation] Small molecule compounds enhance differentiation to hepatocytes from human induced pluripotent stem cells(低分子化合物はヒト人工多能性幹細胞から肝細胞への分化を促進する).2012

    • Author(s)
      近藤祐樹,岩尾岳洋,吉橋幸美,三森佳代,杉山留理,佐々木崇光,永田 清,黒瀬光一,丹羽卓朗,山折 大,大森 栄,中村克徳,松永民秀
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Year and Date
      20121120-22
  • [Presentation] Generation of human induced pluripotent stem cell derived enterocytes with peptide transport function(ペプチド輸送機能を有するヒト iPS 細胞由来腸管細胞の作製)2012

    • Author(s)
      岩尾岳洋,中村克徳,永田 清,松永民秀
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      千葉
    • Year and Date
      20121120-22
  • [Presentation] Differentiation into functional enterocyte-like cells from human induced pluripotent stem cells2012

    • Author(s)
      Takahiro Iwao, Kiyoshi Nagata, Tamihide Matsunaga
    • Organizer
      19th Microsomes and Drug Oxidations (MDO) and 12th European Regional International Society for the Study of Xenobiotics (ISSX) Meeting
    • Place of Presentation
      (Noordwijk aan Zee, The Netherlands).
    • Year and Date
      20120617-21
  • [Presentation] 疾患及び創薬研究の新規材料として期待されるヒト iPS 細胞2012

    • Author(s)
      松永民秀
    • Organizer
      桜山ウイルス研究会(特別講演)
    • Place of Presentation
      名古屋
    • Year and Date
      2012-11-28
  • [Presentation] ヒト人工多能性幹細胞から肝細胞への分化に対する低分子化合物の効果.2011

    • Author(s)
      近藤祐樹,三森佳代,吉橋幸美,杉山留理,岩尾岳洋,黒瀬光一,松永民秀
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-13
  • [Presentation] ヒト人工多能性幹細胞の肝細胞への分化に与えるクエルセチンの効果2011

    • Author(s)
      近藤祐樹,岩尾岳洋,斎藤昌良,丹羽卓朗,黒瀬光一,永田 清,松永民秀
    • Organizer
      日本薬物動態学会第26回年会
    • Place of Presentation
      広島
    • Year and Date
      2011-11-16
  • [Presentation] ヒト ES 及び iPS 細胞の肝細胞への分化と薬物動態試験への応用2011

    • Author(s)
      松永民秀
    • Organizer
      第15回薬物動態談話会セミナー
    • Place of Presentation
      大阪
    • Year and Date
      2011-08-25
  • [Presentation] ヒト人工多能性幹細胞からの肝細胞への効率的な分化方法の検討.2011

    • Author(s)
      近藤祐樹,岩尾岳洋,三森佳代,吉橋幸美,大森 栄,松永民秀
    • Organizer
      第57回日本薬学会東海支部総会・大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-07-09
  • [Presentation] ヒト iPS 細胞の肝細胞様細胞への分化と薬物代謝酵素の発現2011

    • Author(s)
      松永民秀,近藤祐樹,岩尾岳洋,大森 栄
    • Organizer
      日本法中毒学会第30 年会
    • Place of Presentation
      長崎
    • Year and Date
      2011-06-11
  • [Presentation] ヒト人工多能性幹細胞の肝細胞への分化と薬物代謝酵素の発現解析2011

    • Author(s)
      近藤祐樹,鎌田 昇,坂本 栄,松永民秀,大森 栄
    • Organizer
      日本薬学会第131 年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30
  • [Presentation] 正常ヒト胎児肝細胞のCYP3A 発現に及ぼす擬似低酸素誘導化合物デフェロキサミンの影響2011

    • Author(s)
      青沼安希子,鈴木英二,中村克徳,松永民秀,大森 栄
    • Organizer
      日本薬学会第131 年会
    • Place of Presentation
      静岡
    • Year and Date
      2011-03-30

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Published: 2014-08-29  

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