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Elucidation of the mechanism of epithelial stem cell niche and its reproduction

Research Project

Project/Area Number 26462685
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionOsaka University

Principal Investigator

Hayashi Ryuhei  大阪大学, 医学系研究科, 寄附講座准教授 (70535278)

Research Collaborator YAMAMOTO Masayuki  東北大学, メディカル・メガバンク機構, 機構長
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords幹細胞ニッチ / 角膜上皮幹細胞 / N-cadherin / NRF2 / 角膜上皮 / Nrf2 / N-cadherin / Nrf2 / 幹細胞
Outline of Final Research Achievements

In this study, we aimed to elucidate the epithelial stem cell niche using the corneal epithelial stem cells as a model of stem cell niche focusing on N-cadherin and NRF2, and developed a new corneal epithelial culture system-based on the information obtained there. As a result, we clarified a part of the mechanism for regulation of N-cadherin expression, and also showed that this mechanism also contributes to normal differentiation of corneal epithelium. From the results of this research, we successfully differentiated corneal epithelial (stem) cells from pluripotent stem cells. In addition, it was found that activation of NRF2 remarkably increases corneal epithelial stem cell survival activity. Moreover, based on the results of this research, we succeeded in development of conservation method for epithelial stem cells focusing on NRF2 activation mechanism.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (34 results)

All 2017 2016 2015 2014 Other

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 8 results,  Acknowledgement Compliant: 5 results) Presentation (13 results) (of which Int'l Joint Research: 2 results,  Invited: 7 results) Book (10 results) Remarks (1 results)

  • [Journal Article] Coordinated generation of multiple ocular-like cell lineages and fabrication of functional corneal epithelial cell sheets from human iPS cells.2017

    • Author(s)
      Hayashi R, Ishikawa Y, Katori R, Sasamoto Y, Taniwaki Y, Takayanagi H, Tsujikawa M, Sekiguchi K, Quantock AJ, Nishida K.
    • Journal Title

      Nat Protoc.

      Volume: Apr;12(4) Issue: 4 Pages: 683-696

    • DOI

      10.1038/nprot.2017.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Ebselen Preserves Tissue-Engineered Cell Sheets and their Stem Cells in Hypothermic Conditions.2016

    • Author(s)
      Katori R, Hayashi R, Kobayashi Y, Kobayashi E, Nishida K.
    • Journal Title

      Sci Rep.

      Volume: Dec 14;6 Issue: 1 Pages: 38987-38987

    • DOI

      10.1038/srep38987

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Co-ordinated ocular development from hiPSCs and recovery of anterior eye function.2016

    • Author(s)
      Hayashi R, Ishikawa Y, Sasamoto Y, Katori R, Nomura N, Ichikawa T, Araki S, Soma T, Kawasaki S, Sekiguchi K, Quantock A, Tsujikawa M, & Nishida K.
    • Journal Title

      Nature

      Volume: 17;531(7594) Issue: 7594 Pages: 376-80

    • DOI

      10.1038/nature17000

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes.2016

    • Author(s)
      Sasamoto Y, Hayashi R, Park S, Saito-Adachi M, Suzuki Y, Kawasaki S, Quantock A, Nakai K, Tsujikawa M, and Nishida K
    • Journal Title

      Scientific Reports

      Volume: 22;6:20807 Issue: 1 Pages: 20807-20807

    • DOI

      10.1038/srep20807

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of a Corneal Epithelial Cell Sheet from Human Pluripotent Stem Cells by a Method Based on Spontaneous Ocular Cell Differentiation.2016

    • Author(s)
      Hayashi R, Ishikawa Y, Katori R, Taniwaki Y, Quantock A, Tsujikawa M, and Nishida K.
    • Journal Title

      Protocol Exchange

      Volume: 無

    • DOI

      10.1038/protex.2016.009

    • Related Report
      2015 Research-status Report
    • Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Localization and osteoblastic differentiation potential of neural crest-derived cells in oral tissues of adult mice.2015

    • Author(s)
      Ono M
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 464 Issue: 4 Pages: 1209-1214

    • DOI

      10.1016/j.bbrc.2015.07.106

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Acquisition of Infinite Proliferation in a Rabbit Corneal Endothelial Cell Line with Maintenance of Phenotypic and Physiological Characteristics.2015

    • Author(s)
      Kageyama T, Hayashi R, Hara S, Yoshikawa K, Ishikawa Y, Nishida K.
    • Journal Title

      J Tissue Eng Regen Med.

      Volume: 未定

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular and cellular features of murine craniofacial and trunk neural crest cells as stem cell-like cells2014

    • Author(s)
      Kunie Hagiwara, Takeshi Obayashi, Nobuyuki Sakayori, Emiko Yamanishi, Ryuhei Hayashi, Noriko Osumi, Toru Nakazawa, Kohji Nishida
    • Journal Title

      PLoS One

      Volume: 9(1) Issue: 1 Pages: 1-13

    • DOI

      10.1371/journal.pone.0084072

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification and potential application of human corneal endothelial progenitor cells.2014

    • Author(s)
      Hara S, Hayashi R, Soma T, Kageyama T, Duncan T, Tsujikawa M, Nishida K.
    • Journal Title

      Stem Cells Dev.

      Volume: 23 Issue: 18 Pages: 2190-201

    • DOI

      10.1089/scd.2013.0387

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maintenance and distribution of epithelial stem/progenitor cells after corneal reconstruction using oral mucosal epithelial cell sheets.2014

    • Author(s)
      Soma T, Hayashi R, Sugiyama H, Tsujikawa M, Kanayama S, Oie Y, Nishida K.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 10 Pages: e110987-e110987

    • DOI

      10.1371/journal.pone.0110987

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 多能性幹細胞を用いた眼組織分化誘導技術の開発と角膜再生医療への実用化2017

    • Author(s)
      林 竜平
    • Organizer
      日本再生医療学会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞を用いた角膜上皮の分化誘導と再生医療への応用2017

    • Author(s)
      林 竜平
    • Organizer
      角膜カンファレンス
    • Place of Presentation
      アクロス福岡
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養上皮細胞シート保存液のスクリーニング2017

    • Author(s)
      香取良祐、林竜平ら
    • Organizer
      角膜カンファレンス
    • Place of Presentation
      アクロス福岡
    • Related Report
      2016 Annual Research Report
  • [Presentation] Induction of Corneal Epithelial Cells from Human Pluripotent Stem Cells by a Method Based on Spontaneous Ocular Cell Differentiation2016

    • Author(s)
      R. Hayashi et al.
    • Organizer
      ISSCR 2016
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2016-06-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞を用いた細胞自律的な角膜上皮分化誘導と再生医療への実用化2016

    • Author(s)
      林竜平
    • Organizer
      日本再生医療学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-03-19
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 培養上皮細胞シート保存液のスクリーニング2016

    • Author(s)
      香取良祐、林竜平ら
    • Organizer
      日本再生医療学会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトiPS細胞を用いた角膜上皮の再生医療2016

    • Author(s)
      林竜平
    • Organizer
      日本角膜学会
    • Place of Presentation
      軽井沢プリンスホテル
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] iPS細胞を用いた角膜再生治療法の開発2016

    • Author(s)
      林竜平、辻川元一、西田幸二
    • Organizer
      AMED再生医療公開シンポジウム
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2016-01-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ヒトiPS細胞からの協調的な眼組織発生と角膜再生医療への応用2016

    • Author(s)
      林 竜平
    • Organizer
      眼科若手研究者の会
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Induction of Corneal Epithelial Cells from Human Pluripotent Stem Cells by a Method Based on Spontaneous Ocular Cell Differentiation2016

    • Author(s)
      Ryuhei Hayashi, Yuki Ishikawa, Yuzuru Sasamoto, Ryosuke Katori, Tatsuya Ichikawa, Naoki Nomura, Takeshi Soma, Satoshi Kawasaki, Andrew J Quantock, Kiyotoshi Sekiguchi, Motokazu Tsujikawa, and Kohji Nishida
    • Organizer
      ISSCR
    • Place of Presentation
      米国サンフランシスコ
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞からの協調的な眼組織発生と角膜再生医療への応用2016

    • Author(s)
      林 竜平
    • Organizer
      産学連携蛋白質研究所セミナー
    • Place of Presentation
      大阪大学蛋白質研究所
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 幹細胞を用いた角膜再生治療法の開発2015

    • Author(s)
      林竜平
    • Organizer
      第2回COMITシンポジウム
    • Place of Presentation
      大阪大学
    • Year and Date
      2015-08-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] The Role of Nrf2-Mediated Defense System in Corneal Epithelial Wound Healing2014

    • Author(s)
      Ryuhei Hayashi, Noriko Himori, Nakazawa, Masayuki Yamamoto, Kohji Nishida
    • Organizer
      World Ophthalmology Congress
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2014-04-02 – 2014-04-06
    • Related Report
      2014 Research-status Report
  • [Book] iPS細胞の安全・高品質な作製技術2016

    • Author(s)
      石川 幸、林 竜平
    • Total Pages
      5
    • Publisher
      技術情報協会
    • Related Report
      2016 Annual Research Report
  • [Book] 日本眼科学会誌 外国書要覧「ヒトiPS細胞からの協調的な眼組織発生と角膜機能の回復」2016

    • Author(s)
      林 竜平
    • Total Pages
      1
    • Publisher
      日本眼科学会
    • Related Report
      2016 Annual Research Report
  • [Book] 再生医療と疾患解明の鍵となる組織幹細胞2016

    • Author(s)
      林 竜平、西田幸二
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2016 Annual Research Report
  • [Book] 日本の眼科「news & topics 今月の一話」2016

    • Author(s)
      林 竜平、西田幸二
    • Total Pages
      2
    • Publisher
      日本眼科医会
    • Related Report
      2016 Annual Research Report
  • [Book] 『月刊糖尿病』「膵島再生― 膵臓・膵島移植からiPS細胞を用いた膵再生と他の臓器の再生医療まで ―」2016

    • Author(s)
      林 竜平、西田幸二
    • Total Pages
      7
    • Publisher
      医学出版
    • Related Report
      2016 Annual Research Report
  • [Book] 腎と透析2016

    • Author(s)
      林竜平、西田幸二
    • Total Pages
      5
    • Publisher
      株式会社 東京医学社
    • Related Report
      2015 Research-status Report
  • [Book] 月刊糖尿病2016

    • Author(s)
      林竜平、西田幸二
    • Publisher
      医学出版
    • Related Report
      2015 Research-status Report
  • [Book] 医学のあゆみ2015

    • Author(s)
      林竜平、西田幸二
    • Total Pages
      7
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2015 Research-status Report
  • [Book] 実験医学別紙2015

    • Author(s)
      林 竜平
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report
  • [Book] 大阪大学学友会会誌2014

    • Author(s)
      林 竜平
    • Total Pages
      4
    • Publisher
      医学振興銀杏会
    • Related Report
      2014 Research-status Report
  • [Remarks]

    • URL

      http://www.comit.med.osaka-u.ac.jp/jp/news/newsData/news_20170327_1.html

    • Related Report
      2016 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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