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Regenerative medicine for middle ear mucosa - Investigation of optimal cell source to regenerate middle ear aeration-

Research Project

Project/Area Number 18K09357
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionJikei University School of Medicine

Principal Investigator

Yamamoto Yutaka  東京慈恵会医科大学, 医学部, 教授 (10313545)

Co-Investigator(Kenkyū-buntansha) 森野 常太郎  東京慈恵会医科大学, 医学部, 講師 (00796352)
山本 和央  東京慈恵会医科大学, 医学部, 講師 (50408449)
小島 博己  東京慈恵会医科大学, 医学部, 教授 (60234762)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞シート / 中耳再生治療 / 鼻腔粘膜 / 口腔粘膜 / 脂肪由来間葉系幹細胞 / 中耳粘膜 / 再生医療 / 細胞ソース / 口腔粘膜上皮細胞 / 鼻腔粘膜上皮細胞 / 口腔粘膜由来上皮細胞 / 鼻腔粘膜由来線維芽細胞 / 脂肪由来幹細胞 / 経粘膜換気
Outline of Final Research Achievements

Previously, we succeeded to treat middle ears by using nasal mucosal cell sheet. However, it was controversial whether the best cell source of the cell sheet. In this study, we fabricated three types of cell sheet―derived from nasal mucosa, oral mucosa, and adipose derived stem cell of GFP transgenic rat―and transplanted into middle ear cavity of nude rat. The GFP positive transplanted cell sheet derived from nasal mucosal tissue was observed non-keratinized epithelial tissue like as surrounding middle ear mucosal tissue. The results of transplantation of oral mucosal cell sheet, keratinized epithelial tissue was observed. Moreover, the results of transplantation of adipose derived stem cell sheet, hyperostosis-like form was observed in middle ear cavity. We considered that as non-keratinized epithelial regeneration is important to keep or regenerate aeration in middle ear cavity, nasal mucosal cell is the best cell source among these three tissues.

Academic Significance and Societal Importance of the Research Achievements

細胞シートを用いた多くの再生医療では、移植後、移植先の環境に応じる仮説や性質を維持する仮説があり、この解明は大きな課題として掲げられている。本研究では、異なる3ヶ所の細胞ソースから作製した細胞シートを用いて形態に着目して挙動を解析した研究であり、細胞ソースの性質の差異が移植後の効果に大きく反映することを示した。これより、比較的採取可能な部位由来の組織の中で中耳の再生医療には鼻粘膜が適することが確認できたとともに、各治療方法の目的に沿って細胞ソースを選定することに非常に重要な知見となると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (28 results)

All 2020 2019 2018

All Journal Article (11 results) (of which Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (2 results)

  • [Journal Article] Lessons learned from conventional animals: Encouragement to use specific-pathogen-free animals2020

    • Author(s)
      Morino Tsunetaro、Kikuchi Shun、Inagaki Taro、Komori Manabu、Yamamoto Kazuhisa、Kojima Hiromi、Yamato Masayuki
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 296-298

    • DOI

      10.1016/j.reth.2020.03.003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Partial Epithelial?Mesenchymal Transition Was Observed Under p63 Expression in Acquired Middle Ear Cholesteatoma and Congenital Cholesteatoma2019

    • Author(s)
      Takahashi Masahiro、Yamamoto-Fukuda Tomomi、Akiyama Naotaro、Motegi Masaomi、Yamamoto Kazuhisa、Tanaka Yasuhiro、Yamamoto Yutaka、Kojima Hiromi
    • Journal Title

      Otology & Neurotology

      Volume: 40 Issue: 8 Pages: e803-e811

    • DOI

      10.1097/mao.0000000000002328

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Characteristics of Pars Tensa Cholesteatoma: A Comparative Study of Area-Based Classification Systems Proposed by the Japanese Otological Society and the European Academy of Otology & Neuro-Otology2019

    • Author(s)
      Motegi Masaomi、Yamamoto Yutaka、Tada Takeshi、Takahashi Masahiro、Sampei Sayaka、Sano Hiromi、Morino Tsunetaro、Komori Manabu、Miura Masahiro、Yamamoto Kazuhisa、Yaguchi Yuichiro、Sakurai Yuika、Kojima Hiromi
    • Journal Title

      The Journal of International Advanced Otology

      Volume: 15 Issue: 2 Pages: 184-188

    • DOI

      10.5152/iao.2019.6349

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A quantitative study of the suppression of the development of the mastoid air cells by the presence of congenital cholesteatoma2019

    • Author(s)
      Takahashi Masahiro、Yamamoto Yutaka、Koizumi Hiromi、Motegi Masaomi、Komori Manabu、Yamamoto Kazuhisa、Yaguchi Yuichiro、Kojima Hiromi
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 139 Issue: 7 Pages: 557-560

    • DOI

      10.1080/00016489.2019.1606439

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of human nasal mucosal cell sheets fabricated using transported tissue and blood specimens2019

    • Author(s)
      Yoshiyuki Kasai,Tsunetaro Morino,Shun Kikuchi, Ryoto Mitsuyoshi, Masahiro Takahashi,a Kazuhisa Yamamoto,a Yuichiro Yaguchi
    • Journal Title

      Regenerative therapy

      Volume: 11 Pages: 88-94

    • DOI

      10.1016/j.reth.2019.05.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Explant culture of oral mucosal epithelial cells for fabricating transplantable epithelial cell sheet2019

    • Author(s)
      Morino Tsunetaro、Takagi Ryo、Yamamoto Kazuhisa、Kojima Hiromi、Yamato Masayuki
    • Journal Title

      Regenerative Therapy

      Volume: 10 Pages: 36-45

    • DOI

      10.1016/j.reth.2018.10.006

    • NAID

      120006729367

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 鼓室形成術の基本手技(解説)2019

    • Author(s)
      山本 裕
    • Journal Title

      日本耳鼻咽喉科学会会報

      Volume: 22 Pages: 1439-1442

    • Related Report
      2019 Research-status Report
  • [Journal Article] International Collaborative Assessment of the Validity of the EAONO-JOS Cholesteatoma Staging System.2019

    • Author(s)
      James AL, Tono T, Cohen MS, Iyer A, Cooke L, Morita Y, Matsuda K, Yamamoto Y, Sakagami M, Yung M.
    • Journal Title

      Otol Neurotol

      Volume: 40 Issue: 5 Pages: 630-637

    • DOI

      10.1097/mao.0000000000002168

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Explant culture of oral mucosal epithelial cells for fabricating transplantable epithelial cell sheet.2019

    • Author(s)
      Morino T, Takagi R, Yamamoto K, Kojima H, Yamato M.
    • Journal Title

      Regenerative Therapy

      Volume: 10 Pages: 36-45

    • NAID

      120006729367

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nationwide survey of congenital cholesteatoma using staging and classification criteria for middle ear cholesteatoma proposed by the Japan Otological Society2019

    • Author(s)
      Morita Yuka、Tono Tetsuya、Sakagami Masafumi、Yamamoto Yutaka、Matsuda Keiji、Komori Manabu、Hato Naohito、Hashimoto Sho、Takahashi Haruo、Kojima Hiromi
    • Journal Title

      Auris Nasus Larynx

      Volume: 46 Issue: 3 Pages: 346-352

    • DOI

      10.1016/j.anl.2018.10.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] “患者まで届いている再生医療” 中耳粘膜再生治療―培養鼻腔粘膜上皮細胞を用いた日本発の再生医療―2018

    • Author(s)
      森野常太郎, 小島博己
    • Journal Title

      再生医療

      Volume: 17 Pages: 422-428

    • Related Report
      2018 Research-status Report
  • [Presentation] 中耳真珠腫におけるタイトジャンクション関連分子発現の検討2019

    • Author(s)
      高橋 昌寛, 福田 智美, 茂木 雅臣, 穐山 直太郎, 山本 和央, 田中 康広, 山本 裕, 小島 博己
    • Organizer
      第120回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小型霊長類コモンマーモセット側頭骨の解剖学的解析による内耳薬剤投与経路の検討2019

    • Author(s)
      栗原 渉(東京慈恵会医科大学 耳鼻咽喉科), 藤岡 正人, 平林 源希, 小川 郁, 山本 裕, 小島 博己
    • Organizer
      第120回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 弛緩部型真珠腫術後の中耳腔含気についての検討2019

    • Author(s)
      茂木 雅臣, 栗原 渉, 高橋 昌寛, 三瓶 紗弥香, 佐野 博美, 山本 和央, 櫻井 結華, 山本 裕, 小島 博己
    • Organizer
      第120回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 中耳手術 顕微鏡下2019

    • Author(s)
      山本 裕
    • Organizer
      第120回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Round table: Nationwide Survey of Middle Ear Cholesteatoma using Staging and Classification Criteria proposed by the Japan Otological Society2019

    • Author(s)
      Yutaka Yamamoto
    • Organizer
      32th Politzer Society Meeting - 2nd World Congress of Otology
    • Related Report
      2019 Research-status Report
  • [Presentation] テーマセッション: Current state of ossiculoplasty in Japan and clinical factors related to the hearing results2019

    • Author(s)
      Yutaka Yamamoto
    • Organizer
      第29回日本耳科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 教育セミナー : 外耳道後壁削除型鼓室形成術2019

    • Author(s)
      山本 裕
    • Organizer
      第29回日本耳科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 側頭骨手術手技研修WG報告2019

    • Author(s)
      山本 裕
    • Organizer
      第29回日本耳科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 用語委員会報告2019

    • Author(s)
      山本 裕
    • Organizer
      第29回日本耳科学会総会・学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 治験を目指した鼻腔粘膜細胞シートの作製法の検討2019

    • Author(s)
      森野常太郎, 葛西善行, 山本和央, 小島博己
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 培養鼻腔粘膜上皮細胞シートによる中耳粘膜再生を目的とした治療と製造販売に向けた試み2019

    • Author(s)
      小島博己, 山本和央, 森野常太郎, 葛西善行
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Ex vivo studies of the behavior of nasal mucosal cell sheet after grafting2018

    • Author(s)
      Kasai Y, Morino T, Yamamoto K, Kojima H
    • Organizer
      5th Tissue engineering and regenerative medicine international society world congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 培養鼻腔粘膜上皮細胞シートによる中耳粘膜再生治療と製造販売に向けた試み2018

    • Author(s)
      小島博己
    • Organizer
      第28回日本耳科学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 培養上皮細胞シート移植による中耳粘膜再生治療~細胞シート治療の普及に向けた輸送システムの検討~.2018

    • Author(s)
      谷口雄一郎, 山本和央, 森野常太郎, 葛西善行, 稲垣太朗, 小島博己, 肥塚泉
    • Organizer
      第28回日本耳科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 中耳粘膜再生医療の普及に向けた培養鼻粘膜上皮細胞シートの輸送条件の検討2018

    • Author(s)
      森野常太郎, 葛西善行, 山本和央, 谷口雄一郎, 小島博己
    • Organizer
      第28回日本耳科学会
    • Related Report
      2018 Research-status Report
  • [Book] 【耳管のすべて】耳管処置、耳管機能検査のリスクマネージメント2019

    • Author(s)
      森野 常太郎、山本 裕
    • Total Pages
      4
    • Publisher
      JOHNS
    • Related Report
      2019 Research-status Report
  • [Book] 【救急・当直マニュアル-いざというときの対応法】当直での術後急変への対応 耳科手術後の血腫2019

    • Author(s)
      山本 和央、山本 裕
    • Total Pages
      4
    • Publisher
      耳鼻咽喉科・頭頸部外科
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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