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Development of the tolerance induction method by injecting the cultivated donor cells into anterior chamber of the eye

Research Project

Project/Area Number 17K10529
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionMeiji University of Integrative Medicine

Principal Investigator

Yamada Jun  明治国際医療大学, 医学教育研究センター, 教授 (80351352)

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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords角膜移植 / 臓器移植 / 心臓移植 / 角膜内皮細胞 / 免疫寛容 / トレランス / 培養細胞移植 / 前房 / 培養角膜内皮細胞移植 / ACAID / 生体肝移植 / 前房関連免疫偏位 / 移植・再生医療 / 角膜内皮細胞移植
Outline of Final Research Achievements

To establish the tolerance induction method by injecting the cultivated donor cells is the goal of our aim.
Cultivated allogeneic corneal endothelial cell (CEC) injection therapy for CEC dysfunction is now available. To evaluate allogeneic response post CEC injection into the anterior chamber (AC), we developed new experimental models and examined allosensitization and acquisition of transplantation tolerance.Labeled mpCECs in the cryo-injured eyes survived for at least 1 week (N=5). C57BL/6 penetrating keratoplasty allografts at 8-weeks post mpCEC injection never displayed episodes of allogeneic rejection (N=10, 100%, p<0.001). Moreover, more than 50% cardiac allograft survived indefinitely after allogeneic CEC injection. However, other cells including vascular endothelial cells, but not CECs, could not survive anterior chamber of the eye. We need to find the new method for allogeneic tolerance induction.

Academic Significance and Societal Importance of the Research Achievements

アロ移植は基本的に拒絶される。しかし、前房内に移植を行う角膜内皮細胞移植では拒絶されないだけでなく免疫寛容が誘導される。この生体の特殊な応答を臓器移植に応用できた場合には免疫抑制剤の副作用を軽減でき、安全な移植医療が実現できる。マウスモデルにおいて、角膜内皮細胞移植後に全層角膜移植は100%拒絶されなくなり、心臓移植も無治療で生着できることが判明した。人での実現に向けて、角膜移植を用いずに安全な免疫寛容誘導方法を開発することが今後必要であり、あと一歩新たな知見やアイデアが必要である。

Report

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

    (3 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [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] ヒト培養角膜内皮細胞移植後のアロ感作応答の検定技術2019

    • Author(s)
      山田潤, 三好淳一朗, 戸田宗豊, 上原朝子, 上野盛夫, 外園千恵, 木下茂, 羽室淳爾
    • 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
      2019 Annual Research Report 2018 Research-status Report
  • [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, 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 第43回日本角膜学会総会・第35回日本角膜移植学会
    • Related Report
      2019 Annual Research Report 2018 Research-status Report

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

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