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Establishment of an in vivo cell differentiation method that induces an undifferentiated human corneal endothelial subpopulation to mature corneal endothelial cells

Research Project

Project/Area Number 17K11461
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Toda Munetoyo  京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (30550727)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords角膜内皮細胞 / 再生医療 / 移植・再生医療
Outline of Final Research Achievements

In this present study, we successfully established a modified cell expansion method that increases the efficiency of expanding an undifferentiated human corneal endothelial cell (CEC) subpopulation to approximately 1.5 times higher than the previously used method by suppressing the stratification of the cells and the changes to a fibroblast-like morphology. Our novel method successfully expands an undifferentiated human CEC subpopulation by approximately 10,000 times over a 5-week period. Moreover, we found that pretreatment with specific functional low-molecular-weight compounds used for the induction of the differentiation of pluripotent differentiated CECs increases the efficiency of those cells to differentiate to mature CECs. These findings allowed us to successfully establish a cell differentiation method that induces an undifferentiated human CEC subpopulation to mature CECs at an efficiency of approximately 85%.

Academic Significance and Societal Importance of the Research Achievements

一眼から100人水準の増幅であった治験時製法に比べ大幅に増幅効率が改善された。本技術の応用により、Fuchs 角膜ジストロフィー患者を含む300万人以上の潜在患者への適用が可能となり、本邦が世界をリードする革新的角膜移植術である「培養ヒト角膜内皮細胞前房内注入療法」を世界的なレベルにまで発展させることができると期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (3 results)

  • [Journal Article] Metabolites Interrogation in Cell Fate Decision of Cultured Human Corneal Endothelial Cells2020

    • Author(s)
      Hamuro Junji、Numa Kohsaku、Fujita Tomoko、Toda Munetoyo、Ueda Koji、Tokuda Yuichi、Mukai Atushi、Nakano Masakazu、Ueno Morio、Kinoshita Shigeru、Sotozono Chie
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 61 Issue: 2 Pages: 10-10

    • DOI

      10.1167/iovs.61.2.10

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Fluorescence Visualization of Anterior Chamber Injected Human Corneal Endothelial Cells Labeled With Quantum Dots2019

    • Author(s)
      Toda Munetoyo、Yukawa Hiroshi、Yamada Jun、Ueno Morio、Kinoshita Shigeru、Baba Yoshinobu、Hamuro Junji
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 60 Issue: 12 Pages: 4008-4020

    • DOI

      10.1167/iovs.19-27788

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 量子ドット標識ナノ技術による前房内注入培養ヒト角膜内皮細胞の生体内動態の解析2019

    • Author(s)
      戸田宗豊、湯川博、山田潤、上野盛夫、有本知子、外園千恵、馬場嘉信、木下茂、羽室淳爾
    • Organizer
      角膜カンファランス 2019
    • Related Report
      2018 Research-status Report
  • [Presentation] ドナー角膜内皮細胞の健常性に影響を及ぼす要因の探索2019

    • Author(s)
      戸田宗豊、丸山悠子、上原朝子、北澤耕司、上野盛夫、羽室淳爾、外園千恵、木下茂
    • Organizer
      第123回 日本眼科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Factors influencing the health and longevity of donor corneal endothelial cells2019

    • Author(s)
      Munetoyo Toda, Koji Kitazawa, Morio Ueno, Yuko Maruyama, Asako Uehara, Chie Sotozono, Junji Hamuro, and Shigeru Kinoshita
    • Organizer
      Annual meeting of ARVO 2019
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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