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Regeneration of ocular surface specific function and control mechanism by ectopic culture cell transplantation

Research Project

Project/Area Number 17K11488
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionNational Center for Geriatrics and Gerontology (2019)
Kyoto Prefectural University of Medicine (2017-2018)

Principal Investigator

Tsutomu Inatomi  国立研究開発法人国立長寿医療研究センター, 病院, 部長 (00305583)

Co-Investigator(Kenkyū-buntansha) 中村 隆宏  京都府立医科大学, 医学(系)研究科(研究院), 客員講師 (30411078)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords角膜上皮 / 結膜上皮 / 眼表面再建術 / 再生医療 / 培養口腔粘膜上皮移植 / 角膜幹細胞 / 難治性眼表面疾患 / 角膜移植 / 培養角膜上皮移植 / 角膜上皮幹細胞 / 培養口腔粘膜移植 / 眼表面再建 / ムチン / 再生医学 / 細胞・組織
Outline of Final Research Achievements

Cultured corneal and mucosal epithelial transplant have been developed as a new regenerative medicine for severe ocular surface diseases. By extracting stem cells from the corneal limbus or oral mucosal epithelium and inducing cell differentiation, a transplantable stratified epithelial sheet can be prepared and applied to therapy. For binocular diseases, focusing on the autologous oral mucosa and nasal mucosa epithelium makes it possible to restore the ocular surface function without inducing an immune reaction. Ectopically engrafted cells are differentiated while maintaining lineage-based cell characteristics without inducing ocular tissue-specific genes. While being affected by various factors on the ocular surface, it is possible to regenerate the ocular surface structure that substitutes for the corneal tissue, and it has become possible to develop new treatments for severe ocular surface diseases.

Academic Significance and Societal Importance of the Research Achievements

眼表面は視機能維持に重要な役割を果たしており、恒常性と機能は表面を構築する角結膜上皮により維持されている。さまざまな原因によるこれらを構成する上皮幹細胞が消失する角膜上皮幹細胞疲弊症では両眼性に角膜上皮が消失し、高度の視機能障害を来たす。今までの移植医療では拒絶反応や合併症により十分な治療成果が得られない。培養粘膜上皮移植は再生医療を応用することで自家の眼組織や他の粘膜組織から拒絶されない移植医療が可能となり難治性疾患の新しい治療法としての道を拓いている。本研究では眼表面に移植生着した上皮特性や維持メカニズムを解析することで眼表面組織の理解と新しい治療法の開発に貢献する知見が得られた。

Report

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

    (22 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results)

  • [Journal Article] Five-year follow-up outcomes after Descemet's stripping automated endothelial keratoplasty: a retrospective study.2020

    • Author(s)
      Wakimasu K, Kitazawa K, Kayukawa K, Yokota I, Inatomi T, Hieda O, Sotozono C, Kinoshita S
    • Journal Title

      BMJ Open Ophthalmol

      Volume: 5 Pages: 354-354

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk Factors for Corneal Endothelial Cell Loss in Patients with Pseudoexfoliation Syndrome2020

    • Author(s)
      Takanori Aoki, Koji Kitazawa, Tsutomu Inatomi, Natsuki Kusada, Noriko Horiuchi, Kazunori Takeda, Norihiko Yokoi, Shigeru Kinoshita, Chie Sotozono
    • Journal Title

      Sci Rep.

      Volume: 10 Pages: 7260-7260

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Safety of retrocorneal plaque aspiration for managing fungal keratitis.2020

    • Author(s)
      Kitazawa K, Fukuoka H, Inatomi T, Aziza Y, Kinoshita S, Sotozono C.
    • Journal Title

      Jpn J Ophthalmol.

      Volume: 64 Pages: 228-233

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topical ganciclovir treatment post-Descemet's stripping automated endothelial keratoplasty for patients with bullous keratopathy induced by cytomegalovirus.2018

    • Author(s)
      Kitazawa K, Jongkhajornpong P, Inatomi T, Koizumi N, Kayukawa K, Wakimasu K, Sotozono C, Kinoshita S.
    • Journal Title

      Br J Ophthalmol

      Volume: 102 Pages: 1293-1297

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Topical non-steroidal anti-inflammatory drugs for the treatment of cystoid macular edema post Descemet's stripping automated endothelial keratoplasty2018

    • Author(s)
      Kitazawa K, Kayukawa K, Wakimasu K, Inatomi T, Hieda O, Mori K, Sotozono C, Kinoshita S.
    • Journal Title

      Jpn J Ophthalmol

      Volume: 62 Pages: 615-620

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Moderately Long-Term Safety and Efficacy of Repeat Penetrating Keratoplasty.2018

    • Author(s)
      Moderately Long-Term Safety and Efficacy of Repeat Penetrating Keratoplasty.
    • Journal Title

      Cornea

      Volume: 37 Pages: 1255-1259

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy.2018

    • Author(s)
      Kinoshita S, Koizumi N, Ueno M, Okumura N, Imai K, Tanaka H, Yamamoto Y, Nakamura T, Inatomi T, Bush J, Toda M, Hagiya M, Yokota I, Teramukai S, Sotozono C, Hamuro J.
    • Journal Title

      N Engl J Med

      Volume: 378 Pages: 995-1003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The existence of dead cells in donor corneal endothelium preserved with storage media.2017

    • Author(s)
      Kitazawa K, Inatomi T, Tanioka H, Kawasaki S, Nakagawa H, Hieda O, Fukuoka H, Okumura N, Koizumi N, Iliakis B, Sotozono C, Kinoshita S.
    • Journal Title

      Br J Ophthalmol

      Volume: 101 Pages: 1725-1730

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictive clinical factors of cystoid macular edema in patients with Descemet's stripping automated endothelial keratoplasty.2017

    • Author(s)
      Kitazawa K, Kayukawa K, Wakimasu K, Yokota I, Inatomi T, Hieda O, Mori K, Sotozono C, Kinoshita S.
    • Journal Title

      Sci Rep

      Volume: 7 Pages: 7412-7412

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cystoid Macular Edema after Descemet's Stripping Automated Endothelial Keratoplasty.2017

    • Author(s)
      Kitazawa K, Kayukawa K, Wakimasu K, Yokota I, Inatomi T, Hieda O, Mori K, Sotozono C, Kinoshita S.
    • Journal Title

      Ophthalmology

      Volume: 124 Pages: 572-573

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Evolution of cultivated epithelial transplantation in clinical practice.2020

    • Author(s)
      Inatomi T
    • Organizer
      1th Chulalongkorn Eye Center - Kyoto Prefectural University of Medicine joint meeting,
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cell based Therapy for Ocular Surface Reconstruction.2019

    • Author(s)
      Inatomi T
    • Organizer
      SingHealth Duke-NUS Surgical & Aneaesthesa Congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Novel Therapeutic Pathways to Overcome the Challenges of Ocular Surface Reconstruction.2019

    • Author(s)
      Inatomi T
    • Organizer
      Singapore National Eye Center Seminar
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Disease-Specific Endothelial Cell Loss Post DSAEK.2019

    • Author(s)
      Inatomi T
    • Organizer
      APSCRS
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 結膜嚢再建を目的とした培養口腔粘膜上皮移植術の長期術後成績2019

    • Author(s)
      駒井 清太郎,中村隆宏,稲富 勉,木下  茂,外園千恵.
    • Organizer
      第73回日本臨床眼科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] The Importance of Donor Corneal Endothelial Cell Viability for Corneal Transplantation2018

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      World Ophthalmology Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Application of Corneal Regenerative Medicine in Clinical Practice2018

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      6th Asia Cornea Society Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Medical and Surgical Approach for the Treatment of Ocular Cicatricial Pemphigoid2018

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      6th Asia Cornea Society Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Corneal Endothelial Remodeling After DSAEK and DMEK2018

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      6th Asia Cornea Society Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Advanced conjunctival surgery2018

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      American Academy of Ophthalmology
    • Related Report
      2018 Research-status Report
  • [Presentation] Cultivated Oral Mucosal Epithelial Transplantation2017

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      American Society of Cataract and Refractive Surgery
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Advanced Conjunctival Surgery for Cicatrizing Diseases2017

    • Author(s)
      Tsutomu Inatomi
    • Organizer
      American Academy of Opthalmology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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

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