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Development of hybrid corneal tissue transplantation technology using stem cells via genome reprogramming

Research Project

Project/Area Number 16K11332
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionTeikyo University (2017-2018)
Tokyo Women's Medical University (2016)

Principal Investigator

Mimura Tatsuya  帝京大学, 医学部, 准教授 (70463867)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords角膜 / 幹細胞 / メチル化 / エピジェネティクス / 再生
Outline of Final Research Achievements

The purpose of this study is to examine the changes involved in the aging of cells in the cornea. Tissue stem cells from corneal layers were collected by sphere method. We examined the gene expression of stem cells and found that genes such as Nestin, which is a marker for undifferentiated nervous system, were highly expressed. Examination of the methylation of these cells demonstrated a high degree of methylation as compared to normal cultured cells. We could obtained daughter cells, which were high quality cells without shortening the telomere length or without staining with βGAL, from stem cells. We transplanted the regenerated cornea into an rabbit eyes. Transplanted cornea maintained transparency postoperatively. These results suggests that the transplanted undifferentiated cells may be a source of cell proliferation after transplantation.

Academic Significance and Societal Importance of the Research Achievements

培養細胞を移植する報告は各臓器において、研究レベルあるいは臨床レベルで行われている。しかし、移植後に、生着し、そして細胞の供給源にする技術は確立されていなかった。我々が採取した組織幹細胞から得られた前駆細胞は未分化な状態を維持し、しかも動物眼に移植した後も細胞の供給源となり、角膜透明性維持に働いた。分子・遺伝子レベルでは、テロメア長が短縮せず、DNAのメチル化率が低い状態の細胞であることが分かった。本技術を使うことにより、自己の細胞群から選択的に質の良い細胞を採取し、更に自己に戻ることにより疲弊した組織を修復が可能となることが示唆された。また本方法は他の臓器にも応用可能というメリットもある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Invited: 6 results)

  • [Journal Article] Aqueous humor levels of cytokines in patients with age-related macular degeneration2018

    • Author(s)
      Mimura Tatsuya、Funatsu Hideharu、Noma Hidetaka、Shimura Masahiko、Kamei Yuko、Yoshida Maiko、Kondo Aki、Watanabe Emiko、Mizota Atsushi
    • Journal Title

      Ophthalmologica

      Volume: 241 Issue: 2 Pages: 81

    • DOI

      10.1159/000490153

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes of conjunctivochalasis after cataract surgery via a superior transconjunctival sclerocorneal incision2017

    • Author(s)
      1.Mimura T, Iida M, Oshima R, Noma H, Kamei Y, Goto M, Kondo A, Matsubara M.
    • Journal Title

      Int Ophthalmol

      Volume: 37 Issue: 3 Pages: 691

    • DOI

      10.1007/s10792-016-0328-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Silent information regulator T1 in aqueous humor of patients with cataract2016

    • Author(s)
      Kondo A, Goto M, Mimura T, Matsubara M
    • Journal Title

      Clin Ophthalmol.

      Volume: 10 Pages: 307

    • DOI

      10.2147/opth.s100213

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of aflibercept in patients with age-related macular degeneration2016

    • Author(s)
      Okuma,H, Mimura T, Goto M, Kamei Y, Yoshida M, Kondo A, Matsubara M.
    • Journal Title

      Int Ophthalmol

      Volume: 36 Issue: 2 Pages: 159

    • DOI

      10.1007/s10792-015-0089-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 手持ちサイズ・高解像度顕微鏡による眼表面細胞のその場観察2019

    • Author(s)
      三村達哉、溝田淳、西村智
    • Organizer
      角膜カンファランス2019 第43回日本角膜学会総会 第35回日本角膜移植学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 環境因子とアレルギー炎症 ―眼科の立場から2019

    • Author(s)
      三村達哉
    • Organizer
      角膜カンファランス2019 第43回日本角膜学会総会 第35回日本角膜移植学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] AIを用いた、網膜画像診断 今後の活用性について2019

    • Author(s)
      三村達哉
    • Organizer
      眼科勉強会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 角膜の再生治療 ~内皮を中心に~2018

    • Author(s)
      三村達哉
    • Organizer
      第152回帝京大学眼科研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 自動車排ガス由来揮発性有機化合物と加齢黄斑変性の病態との関係2018

    • Author(s)
      三村達哉、松本浩一、浜野茂樹、南波久貴、渡邊恵美子、溝田淳
    • Organizer
      第72回日本臨床眼科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 環境因子と生体反応 総説2018

    • Author(s)
      三村達哉
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 揮発性有機化合物と眼老化2018

    • Author(s)
      三村達哉
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 網膜硝子体の加齢変化とエピジェネティクス2017

    • Author(s)
      三村達哉
    • Organizer
      KOWA 眼疾患勉強会
    • Place of Presentation
      東京都中央区日本橋
    • Year and Date
      2017-02-20
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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