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

Research Project

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
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords薬物動態 / 代謝学 / ヒト人工多能性幹細胞 / iPS細胞 / 肝細胞 / 腸管上皮細胞 / 低分子化合物 / 分化誘導 / 胆管上皮細胞 / ヒトES細胞
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.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (51 results)

All 2013 2012 2011 2010 Other

All Journal Article (15 results) (of which Peer Reviewed: 11 results) Presentation (32 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Hepatocyte Nuclear Factor 6 Activates the Transcription of <i>CYP3A4</i> 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 Metabolism and Pharmacokinetics

      Volume: 28 Issue: 3 Pages: 250-259

    • DOI

      10.2133/dmpk.DMPK-12-RG-132

    • NAID

      130004463310

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Evidence of Pharmacokinetic Changes in Thalidomide Therapy2013

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

      Drug Metabolism and Pharmacokinetics

      Volume: 28 Issue: 1 Pages: 38-43

    • DOI

      10.2133/dmpk.DMPK-12-RV-089

    • NAID

      130004463295

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • 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 Metabolism2013

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

      Biological and Pharmaceutical Bulletin

      Volume: 36 Issue: 2 Pages: 292-298

    • DOI

      10.1248/bpb.b12-00866

    • NAID

      130002480763

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Human Embryonic Stem Cell-derived Hepatocyte-like Cells for Detection of CYP1A Inducers2012

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

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 6 Pages: 598-604

    • DOI

      10.2133/dmpk.DMPK-12-RG-017

    • NAID

      130004933512

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of CYP3A Induction by Glucocorticoids in Human Fetal Liver Cells2012

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

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 6 Pages: 653-657

    • DOI

      10.2133/dmpk.DMPK-12-NT-018

    • NAID

      130004933510

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • 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

    • Related Report
      2012 Final Research Report
    • 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

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lower Expression of HNF4&alpha; and PGC1&alpha; Might Impair Rifampicin-mediated CYP3A4 Induction under Conditions Where PXR Is Overexpressed in Human Fetal Liver Cells2012

    • Author(s)
      Takezawa T
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 4 Pages: 430-438

    • DOI

      10.2133/dmpk.DMPK-11-RG-126

    • NAID

      130004463268

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Hypoxia-inducible Factor-1&alpha; Chemical Stabilizer, CoCl<sub>2</sub> and Hypoxia on Gene Expression of CYP3As in Human Fetal Liver Cells2012

    • Author(s)
      Suzuki E
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 4 Pages: 398-404

    • DOI

      10.2133/dmpk.DMPK-11-RG-074

    • NAID

      130004463262

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Influence of Cytochrome P450 2C19 Gene Variations on Pharmacokinetic Parameters of Thalidomide in Japanese Patients2012

    • Author(s)
      Matsuzawa N, Nakamura K, Matsuda M, Ishida F, Ohmori S
    • Journal Title

      Biol Pharm Bull

      Volume: 35 Pages: 317-320

    • NAID

      130001872311

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 薬物動態研究におけるヒト多能性幹細胞の活用2012

    • Author(s)
      岩尾岳洋、松永民秀
    • Journal Title

      薬剤学

      Volume: 72 Pages: 88-94

    • NAID

      10030452608

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 薬物動態研究における実験材料及び評価系開発の最近の動向2011

    • Author(s)
      松永民秀
    • Journal Title

      Drug Metabo Pharmacokin

      Volume: 26 Pages: 5-6

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 実験材料及び評価系開発の最近の動向(第1回)幹細胞の分化と薬物動態研究への応用ヒトESおよびiPS細胞から肝細胞様細胞および腸管組織への分化誘導2011

    • Author(s)
      岩尾岳洋、松永民秀
    • Journal Title

      Drug Metabol Pharmacokin

      Volume: 26 Pages: 7-14

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Cytochrome P450 3As Gene Expression and Testosterone 6.BETA.-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

      Biological and Pharmaceutical Bulletin

      Volume: 33 Issue: 2 Pages: 249-254

    • DOI

      10.1248/bpb.33.249

    • NAID

      130000156632

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] ES細胞の肝細胞への分化と薬物動態試験への応用2010

    • Author(s)
      松永民秀, 大森栄
    • Journal Title

      医学のあゆみ

      Volume: 232 Pages: 99-109

    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒトiPS細胞由来腸管上皮細胞様細胞におけるUDP-グルクロン酸転移酵素の発現解析2013

    • Author(s)
      畠山和久
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] VEGF添加時期が iPS-sac形成に与える影響の検討2013

    • Author(s)
      大手 万理子
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖原病Ib型患者iPS細胞を用いた遺伝子導入評価系の構築2013

    • Author(s)
      鵜飼 茜
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] iPS細胞由来肝細胞の三次元スフェロイド培養による糖原病Ib型長期遺伝子治療評価系の構築2013

    • Author(s)
      佐藤 大介
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒト人工多能性幹細胞から分化させた肝細胞様細胞による薬物代謝酵素の酵素誘導評価2012

    • Author(s)
      中村克徳、近藤祐樹、杉山留理、相川香織、松永民秀、大森栄
    • Organizer
      日本薬学会第132年回
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-31
    • Related Report
      2011 Annual Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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).
    • Related Report
      2012 Final Research Report
  • [Presentation] ヒトiPS細胞由来肝細胞様細胞におけるUDP-グルクロン酸転移酵素の発現解析2012

    • Author(s)
      畠山 和久
    • Organizer
      第53回(平成24年度) 日本生化学会中国・四国支部例会
    • Place of Presentation
      岡山
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝特異的転写因子HNF-6による薬物代謝酵素発現誘導:新規薬物代謝研究ツールを志向した肝分化iPS 細胞樹立への応用2012

    • Author(s)
      佐々木 崇光
    • Organizer
      平成24 年度 東北薬科大学創薬研究センターシンポジウム
    • Place of Presentation
      仙台
    • Related Report
      2012 Annual Research Report
  • [Presentation] microRNA 導入による肝薬物代謝酵素発現への影響2012

    • Author(s)
      菅野 高弘
    • Organizer
      第51 回日本薬学会東北支部大会
    • Place of Presentation
      青森
    • Related Report
      2012 Annual Research Report
  • [Presentation] HNF6 導入時期による肝分化iPS 細胞の薬物代謝酵素発現へ2012

    • Author(s)
      佐々木 崇光
    • Organizer
      第51 回日本薬学会東北支部大会
    • Place of Presentation
      青森
    • Related Report
      2012 Annual Research Report
  • [Presentation] 糖原病Ib型患者肝非実質由来iPS細胞の樹立と肝臓、好中球への分化誘導及び機能評価2012

    • Author(s)
      佐藤 大介
    • Organizer
      日本人類遺伝学会 第57回大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] 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
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] 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
    • Organizer
      日本薬物動態学会第27回年会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [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
    • Organizer
      第35回 日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [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
    • Organizer
      第35回 日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [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
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] Differentiation into functional enterocyte-like cells from human induced pluripotent stem cells.2012

    • Author(s)
      Iwao T
    • 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
    • Related Report
      2012 Annual Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2012 Final Research Report
  • [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
    • Related Report
      2010 Annual Research Report
  • [Presentation] サルES細胞の肝細胞への分化と薬物動態研究2010

    • Author(s)
      丸山順也, 坂本栄, 松永民秀, 中村克徳, 菊池伸次, 大森栄
    • Organizer
      第25回日本薬物動態学会年会
    • Place of Presentation
      大宮市
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヒトES由来肝細胞のCYP1A誘導剤検出系としての評価2010

    • Author(s)
      土屋広行, 松永民秀, 中村克徳, 市川比奈子, 佐々木克典, 大森栄
    • Organizer
      第25回日本薬物動態学会年会
    • Place of Presentation
      大宮市
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Book] 薬物代謝学医療薬学・医薬品開発の基礎として第3版2010

    • Author(s)
      大森栄(分担執筆)
    • Publisher
      東京化学同人
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.shinshu-u.ac.jp/faculty/medicine/department/master/i-pharra/results.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.shinshu-u.ac.jp/graduate/medicine/master/m-science/yakuzai.html

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.shinshu-u.ac.jp/graduate/medicine/doctoral/m-science/rinsyo.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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