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Establishment of human liver chimeric mice with normal immune system for hepatitis viral infection

Research Project

Project/Area Number 23689040
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionTokai University

Principal Investigator

KAMIYA Akihide  東海大学, 創造科学技術研究機構, 准教授 (30321904)

Co-Investigator(Renkei-kenkyūsha) KAKINUMA Sei  東京医科歯科大学, 分子肝炎制御学講座, 特任講師 (30372444)
Project Period (FY) 2011-11-18 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords肝炎ウイルス / 肝幹細胞 / 多能性幹細胞 / iPS細胞 / 肝前駆細胞 / 肝細胞生物学 / 肝幹・前駆細胞
Research Abstract

Viral hepatitis is a very severe liver disease. Studies for therapies of this disease are difficult because Hepatitis viruses cannot infect to normal experimental animals such as mouse and rat. Thus, we have a plan to establish a new mouse model for the studies of viral hepatitis.
(1) We established a new culture method for the purification and expansion of hepatic progenitor cells derived from human pluripotent cells. These cells are candidate of donor cells into human liver chimera mice.
(2) We tried to transplant primary hepatic progenitor cells derived into neonatal mice. Small numbers of donor cells were detected in the recipient liver and lung.

Report

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

    (40 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (24 results) (of which Invited: 3 results) Book (2 results)

  • [Journal Article] Mesenchymal progenitor cells in mouse fetal liver regulate differentiation and proliferation of hepatoblasts2014

    • Author(s)
      Ito Keiichi, Yanagida Ayaka, Okada Ken, Yamazaki Yuji, Nakauchi Hiromitsu, Kamiya Akihide
    • Journal Title

      Liver international

      Volume: (印刷中) Issue: 9 Pages: 1378-1390

    • DOI

      10.1111/liv.12387

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mesenchymal progenitor cells in mouse fetal liver regulate differentiation and proliferation of hepatoblasts2013

    • Author(s)
      Ito K, Yanagida A, Okada K, Yamazaki Y, Nakauchi H, Kamiya A
    • Journal Title

      Liver Int

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential2013

    • Author(s)
      Yanagida A, Ito K, Chikada H, Nakauchi H, Kamiya A
    • Journal Title

      PLoS One

      Volume: 8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] SALL4, a stem cell biomarker in liver cancers2013

    • Author(s)
      Oikawa T, Kamiya A, Zeniya M, Chikada H, Hyuck AD, Yamazaki Y, Wauthier E, Tajiri H, Miller LD, Wang XW, Reid LM, Nakauchi H
    • Journal Title

      Hepatology

      Volume: 57 Pages: 1469-83

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential.2013

    • Author(s)
      Yanagida A, Ito K, Chikada H, Nakauchi H, Kamiya A.
    • Journal Title

      PLoS One.

      Volume: 8 Issue: 7 Pages: e67541-e67541

    • DOI

      10.1371/journal.pone.0067541

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt5a Signaling Mediates Biliary Differentiation of Fetal Hepatic Stem/Progenitor Cells2013

    • Author(s)
      Kakinuma S, Kiyohashi K, Kamiya A, Sakamoto N, Nitta S, Yamanaka H, YoshinoK, Fujiki J, Murakawa M, Kusano-Kitazume A, Shimizu H, Okamoto R, Azuma S, Nakagawa M, Asahina Y, Tanimizu N, Kikuchi A, Nakauchi H, and *WatanabeM
    • Journal Title

      Hepatology

      Volume: (in press) Issue: 6 Pages: 2502-2513

    • DOI

      10.1002/hep.26293

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prospective Isolation and Characterization of Bipotent Progenitor Cells in Early Mouse Liver Development2012

    • Author(s)
      Okada K, Kamiya A, Ito K, Yanagida A, Ito H, Kondou H, Nishina H, Nakauchi H
    • Journal Title

      Stem Cells Dev

      Volume: 21(7) Pages: 1124-33

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vitro expansion and functional recovery of mature hepatocytes from mouse adult livers2012

    • Author(s)
      Ito H, Kamiya A, Ito K, Yanagida A, Okada K, Nakauchi H
    • Journal Title

      Liver Int

      Volume: 32(4) Pages: 592-601

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sal-like protein 4 (SALL4), a stem cell biomarker in liver cancers.2012

    • Author(s)
      Oikawa T, Kamiya A*, Zeniya M, Chikada H, Hyuck AD, Yamazaki Y, Wauthier E, Tajiri H, Miller LD, Wang XW, Reid LM*, Nakauchi H*.
    • Journal Title

      Hepatology

      Volume: in press Issue: 4 Pages: 1469-83

    • DOI

      10.1002/hep.26159

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of an All-in-One Inducible Lentiviral Vector for Gene Specific Analysis of Reprogramming.2012

    • Author(s)
      Yamaguchi T, Hamanaka S, Kamiya A, Okabe M, Kawarai M, Wakiyama Y, Umino A, Hayama T, Sato H, Lee YS, Kato-Itoh M, Masaki H, Kobayashi T, Yamazaki S, Nakauchi H.
    • Journal Title

      PLoS One.

      Volume: 7 Issue: 7 Pages: e41007-e41007

    • DOI

      10.1371/journal.pone.0041007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly efficient generation of definitive endoderm lineage from human induced pluripotent stem cells2012

    • Author(s)
      Sekine K
    • Journal Title

      Transplant Proc

      Volume: 44(4) Issue: 4 Pages: 1127-1129

    • DOI

      10.1016/j.transproceed.2012.03.001

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro expansion and functional recovery of mature hepatocytes from mouse adult liver2011

    • Author(s)
      Ito H, Kamiya A, Ito K, Yanagida A, Okada K, Nakauchi H
    • Journal Title

      Liver Int

      Volume: 32 Issue: 4 Pages: 592-601

    • DOI

      10.1111/j.1478-3231.2011.02741.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prospective isolation and characterization of bi-potent progenitor cells in early mouse liver development2011

    • Author(s)
      Okada K, Kamiya A, Ito K, Yanagida A, Ito H, Kondou H, Nishina H, Nakauchi H
    • Journal Title

      Cells Dev

      Volume: (Epub ahead of print) Issue: 7 Pages: 1124-33

    • DOI

      10.1089/scd.2011.0229

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice2011

    • Author(s)
      Onozuka I, Sakamoto N, Nakagawa M, Watanabe M, et al.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 406 Issue: 1 Pages: 134-140

    • DOI

      10.1016/j.bbrc.2011.02.012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肝臓における薬物代謝の性差を制御する分子メカニズム2014

    • Author(s)
      近田裕美、坂本明美、徳久剛史、紙谷聡英
    • Organizer
      第13回日本再生医療学会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト多能性幹細胞からのin vitro胆管組織誘導系の構築2014

    • Author(s)
      紙谷聡英、近田裕美、鶴谷康太、柳田絢加、中内啓光
    • Organizer
      第13回日本再生医療学会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] HLH型転写因子による胎生肝幹・前駆細胞の分化誘導2013

    • Author(s)
      近田裕美、紙谷聡英
    • Organizer
      第12回日本再生医療学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2013-03-23
    • Related Report
      2013 Final Research Report
  • [Presentation] In vitro generation and expansion of bi-potent hepatic progenitor-like cells from human iPS cells2013

    • Author(s)
      柳田絢加、伊藤慶一、近田裕美、中内啓光、紙谷聡英
    • Organizer
      第20回肝細胞研究会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2013 Final Research Report
  • [Presentation] Mesenchymal progenitor cells in mouse fetal liver regulate differentiation and proliferation of hepatoblasts2013

    • Author(s)
      伊藤慶一、柳田絢加、中内啓光、紙谷聡英
    • Organizer
      第20回肝細胞研究会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト多能性幹細胞からの二方向性分化能を有する肝前駆細胞の誘導2013

    • Author(s)
      紙谷聡英、中内啓光
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      京王プラザホテル
    • Related Report
      2013 Final Research Report
  • [Presentation] REGULATION OF CYTOCHROME p450 3A11 EXPRESSION IN MOUSE HEPATIC PROGENITOR CELLS BY BCL-62013

    • Author(s)
      Hiromi Chikada, Keiichi Ito, Ayaka Yanagida, Hiromitsu Nakauchi, Akihide Kamiya
    • Organizer
      The 11th Annual Meeting of International Society for Stem Cell
    • Place of Presentation
      Reasearch Boston Convention and Exhibition Center,USA
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト多能性幹細胞からの二方向性分化能を有する肝前駆細胞の誘導2013

    • Author(s)
      紙谷聡英、中内啓光
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2013 Annual Research Report
  • [Presentation] REGULATION OF CYTOCHROME p450 3A11 EXPRESSION IN MOUSE HEPATIC PROGENITOR CELLS BY BCL-62013

    • Author(s)
      Hiromi Chikada, Keiichi Ito, Ayaka Yanagida, Hiromitsu Nakauchi, Akihide Kamiya
    • Organizer
      11th Annual Meeting of International Society of Stem Cell Reseach
    • Place of Presentation
      Boston Convention and Exhibition Center, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] An in vitro expansion system in generating purified hepatic stem/progenitor-like cells derived from human iPS cells2012

    • Author(s)
      紙谷聡英、伊藤慶一、柳田絢加、中内啓光
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] MEK-ERKシグナル経路による肝幹・前駆細胞の増殖制御機構2012

    • Author(s)
      紙谷聡英、伊藤慶一、柳田絢加、中内啓光
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌医科大学
    • Year and Date
      2012-06-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝幹・前駆細胞の長期増殖を制御する細胞内シグナル伝達機構2012

    • Author(s)
      紙谷聡英
    • Organizer
      第11回日本再生医療学会ランチョンセミナー
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2012-06-14
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] The Application of Human iPS cells as an in vitro expansion system in generating purified Hepatic stem/progenitor-like cells to determine the molecular mechanisms regulating human liver orgagenesis2012

    • Author(s)
      柳田絢加、紙谷聡英、伊藤慶一、中内啓光
    • Organizer
      The 10th International Society of Stem Cell Research
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2012-06-14
    • Related Report
      2013 Final Research Report
  • [Presentation] MEK activity regulates stem/progenitoer potential of fetal hepatoblasts through induction of cell cycle arrest2012

    • Author(s)
      紙谷聡英、伊藤慶一、柳田絢加、中内啓光
    • Organizer
      The 10th International Society of Stem Cell Research
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2012-06-14
    • Related Report
      2013 Final Research Report
  • [Presentation] MEK-ERKシグナル伝達系による胎生肝幹・前駆細胞の増殖制御機構2012

    • Author(s)
      紙谷聡英、中内啓光
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      ホテル日航金沢
    • Year and Date
      2012-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] MEK activity regulates stem/progenitoer potential of fetal hepatoblasts through induction of cell cycle arrest2012

    • Author(s)
      Akihide Kamiya
    • Organizer
      第10回 ISSCR
    • Place of Presentation
      横浜・パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト多能性幹細胞からの肝幹・前駆細胞分化誘導系の構築2011

    • Author(s)
      紙谷聡英、中内啓光
    • Organizer
      第15回肝臓学会大会(JDDW2011)
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] 胎仔肝幹細胞の自己複製を制御する新規分子の探索とその機能解明2011

    • Author(s)
      伊藤慶一、紙谷聡英、岡田健、柳田絢加、伊東秀典、中内啓光
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Related Report
      2013 Final Research Report
  • [Presentation] 発生過程におけるcdk抑制因子p57による肝増殖制御機構2011

    • Author(s)
      柳田絢加,紙谷聡英,岡田健,伊藤慶一,伊東秀典,中内啓光
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト多能性幹細胞からの長期増殖可能な肝前駆細胞の分化誘導2011

    • Author(s)
      紙谷聡英、柳田絢加、岡田健、伊藤慶一、中内啓光
    • Organizer
      第18回肝細胞研究会
    • Place of Presentation
      東京ガーデンパレス
    • Related Report
      2013 Final Research Report
  • [Presentation] Prospective isolation and expansion of hepatoblast during early-fetal liver development in mice2011

    • Author(s)
      Okada Ken, Kamiya Akihide, Ito Keiichi, Yanagida Ayaka, Ito Hidenori, Kondou Hiroki, Nishina Hiroshi and Nakauchi Hiromitsu
    • Organizer
      The 9th Annual Meeting of International Society for Stem Cell
    • Place of Presentation
      Reasearch Toronto
    • Related Report
      2013 Final Research Report
  • [Presentation] MEK-ERKシグナル伝達系による胎生肝幹・前駆細胞の増殖制御機構

    • Author(s)
      紙谷聡英
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢・ホテル日航金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝幹・前駆細胞の長期増殖を制御する細胞内シグナル伝達機構

    • Author(s)
      紙谷聡英
    • Organizer
      第11回日本再生医療学会(ランチョンセミナー)
    • Place of Presentation
      横浜・パシフィコ横浜
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] An in vitro expansion system in generating purified hepatic stem/progenitor-like cells derived from human iPS cells.

    • Author(s)
      紙谷聡英
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡・福岡国際会議場
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Book] 肝臓の再生医療に向けた幹細胞研究の進展」In The Frontiers in Life Sciences"幹細胞研究と再生医療"2013

    • Author(s)
      紙谷聡英、近田裕美(中内博光編)
    • Related Report
      2013 Final Research Report
  • [Book] 「肝臓の再生医療に向けた幹細胞研究の進展」 In The Frontiers in Life Sciences “幹細胞研究と再生医療“ (中内博光 編)2013

    • Author(s)
      紙谷聡英、近田裕美
    • Publisher
      南山堂
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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