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Paracrine interactions among human cultured corneal endothlial cells regulated the ce state transition in a paracrine fashion

Research Project

Project/Area Number 26293376
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Kinoshita Shigeru  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30116024)

Co-Investigator(Kenkyū-buntansha) 羽室 淳爾  京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (80536095)
上野 盛夫  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40426531)
奥村 直毅  同志社大学, 生命医科学部, 准教授 (10581499)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords角膜内皮細胞 / 再生医療 / エキソゾーム / miRNA / SASP / CD44 / フックス角膜ジストロフィー / フックス角膜内皮ジストロフィー / 眼細胞生物学 / ヒト角膜内皮細胞 / 細胞相転移 / 細胞外微粒子 / メタボローム
Outline of Final Research Achievements

MiRs in culture supernatants of HCECS were different from those selected in cHCECs. miR146, 34a, and 378 were the representatives of the latter. CD44 is the key to distinguishing differentiated cHCECs from either un-differentiated or cHCECs with CST. The miR378 showed the gradual decrease in parallel with decreases of CD44 expression. Of note, CD44 might be repressed by wild-type p53.
It is intriguing that the selected secreted miRs by comparison of mature differentiated cHCECs versus cHCECS with senescent-like CST or versus cHCECs with distinct CD44 expression levels were mutually not overlapped,thus implicat- ing the distinct role in the maintenance of culture homeostasis. The observed elevated secretion of exosomes in CST-cHCECs might be under the regulation of p53. In regard to the secreted miRs, one of the most relevant issues that remains elusive is whether these secreted miRs are released from, and act on cHCECs as inclusion molecules in exosomes.

Report

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

    (20 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Production of Homogeneous Cultured Human Corneal Endothelial Cells Indispensable for Innovative Cell Therapy.2017

    • Author(s)
      Toda M, Ueno M, Hiraga A, Asada K, Montoya M, Sotozono C, Kinoshita S, Hamuro
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 58 Issue: 4 Pages: 2011-2020

    • DOI

      10.1167/iovs.16-20703

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human Corneal Endothelial Cells.2016

    • Author(s)
      Hamuro J, Toda M, Asada K, Hiraga A, Schlötzer-Schrehardt U, Montoya M,
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 57 Issue: 11 Pages: 4749-4761

    • DOI

      10.1167/iovs.16-19770

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] MicroRNA Profiles Qualify Phenotypic Features of Cultured Human Corneal Endothelial Cells.2016

    • Author(s)
      Ueno M, Asada K, Toda M, Hiraga A, Montoya M, Sotozono C, Kinoshita S, Hamuro
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 57 Issue: 13 Pages: 5509-5517

    • DOI

      10.1167/iovs.16-19804

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 8.Metabolic Plasticity in Cell State Homeostasis and Differentiation of Cultured Human Corneal Endothelial Cells.2016

    • Author(s)
      Hamuro J, Ueno M, Asada K, Toda M, Montoya M, Sotozono C, Kinoshita S.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 57 Issue: 10 Pages: 4452-4463

    • DOI

      10.1167/iovs.16-19807

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Medical Science and Future Realities in Corneal Regenerative Medicine (Fridenwald Award Lecture)2016

    • Author(s)
      Kinoshita S.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of mitochondrial respiration under cell culture stress in human corneal endothelial cells.2016

    • Author(s)
      Kinoshita S,Ueno M,Asada K,Toda M,Nagata K ,Sotozono C,Kosaka N,Ochiya T,Hamuro J.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Metabolic plasticity in the cell-state homeostasis and differentiation of cultured human corneal endothelial cells.2016

    • Author(s)
      Hamuro J,Ueno M,Asada K,Toda M,Montoya M,Sotozono C,Kinoshita S.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of dysregulated expression of miRs in the pathogenesis of bullous keratopathy and Fuchs' endothelial corneal dystrophy.2016

    • Author(s)
      Asada K,Ueno M,Toda M,Hiraga A,Montoya M,Sotozono C,Kinoshita S,Hamuro J.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Profiles of cytokines in the aqueous humor and serum of bullous keratopathy patients.2016

    • Author(s)
      Ueno M, Toda M, Hiraga A, Wakimasu K, Koizumi N, Okumura N, Kazuko A, Sotozono C, Hamuro J, KInoshita S.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The cell homogeneity is indispensable for regenerative medicine by cultivated human corneal endothelial cells.2016

    • Author(s)
      Toda M, Ueno M, Hiraga A, Asada K, Montoya M, Cotozono C, Kinoshita S, Hamuro J.
    • Organizer
      ARVO 2016 Annual Meeting
    • Place of Presentation
      Seattle, WA, USA
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Concomitant evaluation of a panel of exosome proteins and miRs for qualification of cultured human corneal endothelial cells.2016

    • Author(s)
      Ueno M, Asada K, Toda M, Nagata K, Sotozono C, Kosaka N, Ochiya T, Kinoshita S, Hamuro J.
    • Organizer
      ISEV2016 Annual Meeting
    • Place of Presentation
      Rotterdam, Netherlands
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MiRNA profiles qualify epigenetic features of human corneal endothelial cells.2016

    • Author(s)
      羽室淳爾, 上野盛夫, 浅田和子, 戸田宗豊, 外園千恵, 木下茂.
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] 水疱性角膜症患者の血清中および前房水中サイトカインプロファイルの検討.2016

    • Author(s)
      上野盛夫, 戸田宗豊, 平賀朝子, 小泉範子, 奥村直毅, 浅田和子, 外園千恵, 羽室淳爾, 木下茂.
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養ヒト角膜内皮細胞亜集団の特性解析.2016

    • Author(s)
      戸田宗豊, 上野盛夫, 平賀朝子, 浅田和子, 外園千恵, 木下茂, 羽室淳爾.
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] 角膜内皮細胞機能不全におけるepigeneticな細胞機能制御.2016

    • Author(s)
      浅田和子, 上野盛夫, 戸田宗豊, 平賀朝子, 落合孝広, 外園千恵, 木下茂, 羽室淳爾.
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Related Report
      2016 Annual Research Report
  • [Presentation] Analysis of cytokines in serum and aqueous humor in patients with bullous keratopathy.2015

    • Author(s)
      Morio Ueno, Munetoyo Toda, Asako Hiraga, Naomi Tobita, Hiroko Nakagawa, Chie Sotozono, Noriko Koizumi, Kazuko Asada, Junji Hamuro, Shigeru Kinoshita.
    • Organizer
      ARVO2016
    • Place of Presentation
      Denver
    • Year and Date
      2015-05-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Investigation of the donor tissue information on the phenotypes of cultivated human corneal endothelium.2015

    • Author(s)
      2.Hiroshi Tanaka, Morio Ueno, Munetoyo Toda, Junji Hamuro, Kengo Yoshii, Noriko Koizumi, Naoki Okumura, Shigeru Kinoshita, Monty Montoya, Bernie Iliakis.
    • Organizer
      ARVO2016
    • Place of Presentation
      Denver
    • Year and Date
      2015-05-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Novel Treatment Dimensions for Corneal Endothelial Dysfunction.2015

    • Author(s)
      Shigeru Kinoshita
    • Organizer
      Charles D. Kelman Innovator's Lecture, ASCRS2015
    • Place of Presentation
      San Diego
    • Year and Date
      2015-04-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] 再生医療・細胞治療のための細胞加工物評価技術,第7章培養細胞の均質性検査2016

    • Author(s)
      羽室淳爾(分担) 佐藤陽治(監修)
    • Total Pages
      10
    • Publisher
      シーエムシー出版
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] HUMAN FUNCTIONAL CORNEAL ENDOTHELIAL CELL AND APPLICATION THEREOF2017

    • Inventor(s)
      木下茂、外園千恵、上野盛夫、羽室淳爾
    • Industrial Property Rights Holder
      京都府立医科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017-02-15
    • Related Report
      2016 Annual Research Report

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

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