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Development of transplantation of hepatocytes produced from iPS cells to liver failure

Research Project

Project/Area Number 23591002
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research Institution独立行政法人国立病院機構 下志津病院(臨床研究部)

Principal Investigator

TOMIZAWA Minoru  独立行政法人国立病院機構下志津病院(臨床研究部), その他部局等, その他 (90334193)

Co-Investigator(Renkei-kenkyūsha) OHIRA Miki  千葉県がんセンター(研究所), がんゲノムセ ンター・がんゲノム研究室, 室長 (20311384)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsiPS cells / 肝細胞 / 転写因子 / 増殖因子 / 糖新生 / 尿素サイクル / iPS細胞 / cDNAマイクロアレイ / ブドウ糖 / アルギニン / 肝前駆細胞 / リアルタイム定量PCR
Research Abstract

A medium with Activin A was developed for feeder-free culture of iPS cells. iPS cells differentiated to hepatoblasts from iPS cells transfected with C/EBP alpha, GATA4, HEX, and FoxA2 in a medium with Oncostatin M, EGF, and RA. Hepatocyte selection medium was developed without glucose or arginine, supplemented with galactose and ornithine. When HSM was added to co-culture of iPS cells and human primary hepatocytes, iPS cells died and hepatocytes survived. Hepatocytes were successfully purified.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (38 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 6 results) Presentation (15 results) Book (2 results) Patent(Industrial Property Rights) (7 results) (of which Overseas: 5 results)

  • [Journal Article] Frizzled-2: A potential novel target for molecular pancreatic cancer therapy2014

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, YoshidaT.
    • Journal Title

      Oncology Lett

      Volume: 7 Pages: 74-78

    • Related Report
      2013 Final Research Report
  • [Journal Article] Frizzled-2: A potential novel target for molecular pancreatic cancer therapy.2014

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, YoshidaT
    • Journal Title

      Oncology Lett

      Volume: 7 Issue: 1 Pages: 74-78

    • DOI

      10.3892/ol.2013.1681

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activin A is essential for feeder-free culture of human induced pluripotent stem cells2013

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T.
    • Journal Title

      J Cell Biochem

      Volume: 114 Pages: 584-588

    • Related Report
      2013 Final Research Report
  • [Journal Article] Survival of primary human hepatocytes and death of induced pluripotent stem cells in media lacking glucose and arginine2013

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T.
    • Journal Title

      PLoS ONE

      Volume: 8

    • Related Report
      2013 Final Research Report
  • [Journal Article] Niclosamide suppresses hepatoma cell proliferation via the Wnt pathway2013

    • Author(s)
      Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T.
    • Journal Title

      OncoTargets and Therapy

      Volume: 6 Pages: 1685-1693

    • Related Report
      2013 Final Research Report
  • [Journal Article] Survival of primary human hepatocytes and death of induced pluripotent stem cells in media lacking glucose and arginine.2013

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 8 Pages: e71897-e71897

    • DOI

      10.1371/journal.pone.0071897

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Niclosamide suppresses hepatoma cell proliferation via the Wnt pathway.2013

    • Author(s)
      Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T
    • Journal Title

      OncoTargets and Therapy

      Volume: 6 Pages: 1685-1693

    • DOI

      10.2147/ott.s50065

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single-step protocol for the differentiation of human induced pluripotent stem cells into hepatic progenitor-like cells2012

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T.
    • Journal Title

      Biomed Rep

      Volume: 1 Pages: 18-22

    • Related Report
      2013 Final Research Report
  • [Journal Article] Insulin-like growth factor I receptor involvement in proliferation of NOR-P1 cells in serum-free media2012

    • Author(s)
      Tomizawa M., Shinozaki F., Sugiyama T., Yamamoto S., Sueishi M., Yoshida T.
    • Journal Title

      J Cell Biochem

      Volume: 113 Pages: 2714-2720

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Journal Article] Plasmid DNA introduced into cultured cells with diagnostic ultrasound2012

    • Author(s)
      Tomizawa M., Shinozaki F., Sugiyama T., Yamamoto S., Sueishi M., Yoshida T.
    • Journal Title

      Oncology Rep

      Volume: 27 Pages: 1360-1364

    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Journal Article] Single-step protocol for the differentiation of human induced pluripotent stem cells into hepatic progenitor-like cells.2012

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T
    • Journal Title

      Biomed Rep

      Volume: 1 Pages: 18-22

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activin A is essential for feeder-free culture of human induced pluripotent stem cells2012

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T
    • Journal Title

      J Cell Biochem

      Volume: 114 Issue: 3 Pages: 584-588

    • DOI

      10.1002/jcb.24395

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activin A maintains pluripotency markers and proliferative potential of human induced pluripotent stem cells2011

    • Author(s)
      Tomizawa, M., Shinozaki, F., Sugiyama, T., Yamamoto, S., Sueishi, M., and Yoshida, T.
    • Journal Title

      Exp Therap Med

      Volume: 2 Pages: 405-408

    • Related Report
      2013 Final Research Report
  • [Journal Article] Activin A maintains pluripotency markers2011

    • Author(s)
      Tomizawa M, Shinozaki F, at al.
    • Journal Title

      Exp Therap Med

      Volume: 2 Pages: 405-408

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] iPS細胞が死滅し初代培養肝細胞が生存する培地2014

    • Author(s)
      富澤稔、篠崎文信、本吉慶史、杉山隆夫、山本重則、末石眞
    • Organizer
      第13回日本再生医療学会総会
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] iPS細胞が死滅し肝細胞が生存する培地の開発2013

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第12回日本再生医療学会総会
    • Related Report
      2013 Final Research Report
  • [Presentation] iPS細胞が死滅し肝細胞が生存する培地の開発2013

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第49回日本肝臓学会総会
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] iPS細胞が死滅し肝細胞が生存する培地2013

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第17回日本肝臓学会大会
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] iPS細胞から肝細胞分化を目指した転写因子の解析2012

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第98回日本消化器病学会総会
    • Related Report
      2013 Final Research Report
  • [Presentation] Activin Aを主体とするヒトiPS細胞の無フィーダー培地の開発2012

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第11回日本再生医学会総会
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒトiPS細胞においてSox17の発現を亢進させる増殖因子の検討2012

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第16回日本肝臓学会大会
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝細胞分化を目指したヒトiPS細胞に対する増殖因子の分化誘導能の検討2011

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第15回日本肝臓学会大会
    • Related Report
      2013 Final Research Report
  • [Presentation] Induced pluripotent stem cells maintained pluripotency markers with Activin A in feeder free culture

    • Author(s)
      Tomizawa, M., Shinozaki, F,. Sugiyama, T., Yamamoto, S., Sueishi, M., Yoshida, T.
    • Organizer
      10th Annual Meeting of International Society of Stem Cell Research (ISSCR)
    • Related Report
      2013 Final Research Report
  • [Presentation] iPS細胞から肝細胞分化を目指した転写因子の解析

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第98回日本消化器病学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Activin Aを主体とするヒトiPS細胞の無フィーダー培地の開発

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第11回日本再生医学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Induced pluripotent stem cells maintained pluripotency markers with Activin A in feeder free culture

    • Author(s)
      Tomizawa, M., Shinozaki, F,. Sugiyama, T., Yamamoto, S., Sueishi, M., Yoshida, T
    • Organizer
      10th Annual Meeting of International Society of Stem Cell Research (ISSCR)
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒトiPS細胞においてSox17の発現を亢進させる増殖因子の検討

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第16回日本肝臓学会大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] iPS細胞が死滅し肝細胞が生存する培地の開発

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 肝細胞分化を目指したヒトiPS細胞に対する増殖因子の分化誘導能の検討

    • Author(s)
      富澤稔、篠崎文信、杉山隆夫、山本重則、末石眞、吉田孝宣
    • Organizer
      第15回日本肝臓学会大会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Book] Induced pluripotent stem cells as a source of hepatocytes. In : Pluripotent stem cells, ed. Deepa Bhartiya and Nibedita Lenka, Rijeka, Croatia2013

    • Author(s)
      Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T.
    • Publisher
      InTech
    • Related Report
      2013 Final Research Report
  • [Book] Pluripotent stem cells2013

    • Author(s)
      4. Tomizawa M, Shinozaki F, Sugiyama T, Yamamoto S, Sueishi M, Yoshida T
    • Total Pages
      12
    • Publisher
      InTech
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 胚性幹細胞から肝芽細胞を得る方法2013

    • Inventor(s)
      富澤稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-05-02
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 多能性幹細胞から肝前駆細 胞への分化誘導方法2012

    • Inventor(s)
      富澤稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-080708
    • Filing Date
      2012-03-30
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Composition for culturing pluripotent stem cells and use thereof2012

    • Inventor(s)
      富澤稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-06-28
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 人工多能性幹細胞から分化した 肝細胞を含む細胞群から、肝細胞からなる 細胞培養物を得る方法2012

    • Inventor(s)
      富澤稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-286978
    • Filing Date
      2012-12-28
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 国際特許出願2012

    • Inventor(s)
      富澤 稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-06-28
    • Related Report
      2012 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 特許出願2012

    • Inventor(s)
      富澤 稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-286978
    • Filing Date
      2012-12-28
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] ヒト多能性幹細胞から肝前駆細胞への分化誘導法2012

    • Inventor(s)
      富澤稔
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Number
      2012-080708
    • Filing Date
      2012
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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