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Acceleration of wound healing after laryngotracheal mucosal injury

Research Project

Project/Area Number 18K09345
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKagoshima University (2020-2022)
Shizuoka Prefectural Hospital Organization (2019)
Kyoto University (2018)

Principal Investigator

YAMASHITA MASARU  鹿児島大学, 医歯学域医学系, 教授 (10635519)

Co-Investigator(Kenkyū-buntansha) 末廣 篤  京都大学, 医学研究科, 特定講師 (00738247)
大森 孝一  京都大学, 医学研究科, 教授 (10233272)
楯谷 一郎  藤田医科大学, 医学部, 教授 (20526363)
岸本 曜  京都大学, 医学研究科, 助教 (80700517)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords喉頭 / 声帯 / 気管 / 粘膜上皮 / 粘膜再生 / 上気道 / 感染制御 / 悪性腫瘍 / 上気道傷害 / 気道組織再生 / 気道組織修復 / 気管再生 / 成長因子 / 線毛運動評価 / 喉頭再生 / 喉頭気管損傷モデル / 気道粘膜維持・修復機構 / 喉頭気管傷害モデル / 内視鏡下声帯粘膜損傷モデル / 喉頭気管 / 粘膜傷害 / 創傷治癒
Outline of Final Research Achievements

We investigated the restoration mechanism from damage to the laryngo-tracheal mucosa.
Analysis of recovery status of tight junctions after vocal fold mucosal injury, suppression of Serpinh1 by siRNA aiming at recovery from vocal fold mucosal fibrosis, analysis of cell polarity maintenance mechanism of tracheal mucosal epithelium, investigation of collagen sponge containing various growth factors aiming functional regeneration of tracheal epithelium, and analysis of macrophage polarity after vocal mucosal injury were performed.In addition, iPS cell-derived multiciliated epithelial cells were seeded on artificial trachea and engraftment experiments were performed in rats. We also established an analyzing method for live tracheal epithelial cilia, developed an organ culture evaluation system for trachea using IGF, and conducted experiments to clarify the role of phosphorylcholine in streptococcal adhesion to epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

喉頭・気管の粘膜上皮は外傷、炎症、悪性腫瘍手術などによって傷害され、気道という生命に直結する組織であるため、早期の機能的粘膜上皮の再生が望まれている。今回の様々な研究結果により、粘膜傷害によって変化する因子やその評価方法、修復・再生の促進法に関しての糸口が得られた。
各実験結果を組み合わせたり、さらに深めた研究を遂行することにより、気道粘膜傷害後の喀痰排出能や音声の維持、誤嚥の防止などに寄与する可能性がある。喉頭分泌腺や傷害された筋肉再生などについてはまだまだ解析が進んでいないこともあり、最終的には臓器そのものの修復・再生を目指して今後も研究を継続していく予定である。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (26 results)

All 2023 2022 2021 2020 2019 2018 2017

All Journal Article (17 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 16 results,  Open Access: 5 results) Presentation (9 results) (of which Invited: 1 results)

  • [Journal Article] The Usefulness of Machine Learning Based Evaluation of Clinical and Pretreatment [18 F]FDG PET/CT Radiomic Features for Predicting Prognosis in Hypopharyngeal Cancer2023

    • Author(s)
      Nakajo M, Nagano H, Jinguji M, Mukai A, Kawabata H, Tani A, Hirahara D, Yamashita M, Yoshiura T
    • Journal Title

      Molecular Imaging and Biology

      Volume: 25(2) Issue: 2 Pages: 303-313

    • DOI

      10.1007/s11307-022-01757-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of endoscopic ultrasonography in evaluating tumor thickness in patients with superficial pharyngeal carcinoma: A pilot study2022

    • Author(s)
      Maeda H, Sasaki F, Kabayama M, Iwaya H, Komaki Y, Arima S, Tanoue S, Hashimoto S, Kanmura S, Miyashita K, Ohori J, Yamashita M, Ido A
    • Journal Title

      Auris Nasus Larynx

      Volume: 49(3) Issue: 3 Pages: 495-503

    • DOI

      10.1016/j.anl.2021.11.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Phosphorylcholine Expression on the Adherence and Invasion of Streptococcus pyogenes to Epithelial Cells2022

    • Author(s)
      Iuchi H, Ohori J, Matsuzaki H, Tokushige T, Toge S, Yamashita M
    • Journal Title

      Microorganisms

      Volume: 10(3) Issue: 3 Pages: 527-527

    • DOI

      10.3390/microorganisms10030527

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 含嗽の細菌付着上皮細胞の除去作用に関する研究2022

    • Author(s)
      黒野 祐一、井内 寛之、山下 勝
    • Journal Title

      日本耳鼻咽喉科学会会報

      Volume: 125 Pages: 279-284

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transplantation of human iPS cell-derived airway cells on vitrigel membrane into rat nasal cavity2021

    • Author(s)
      Kuwata F, Ohnishi H, Yamamoto N, Takezawa T, Yamashita M, Okuyama H, Hayashi Y, Yoshimatsu M, Kitada Y, Tada T, Kobayashi M, Omori K
    • Journal Title

      Tissue Eng Part A

      Volume: Nov.27

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of antibacterial agents against cell-invading bacteria such as Streptococcus pyogenes and Haemophilus influenzae2021

    • Author(s)
      IuchiH, Ohori J, Kiyama S, Imura N, Nishi J, Kurono Y, Yamashita M
    • Journal Title

      BMC Microbiology

      Volume: 21 Issue: 1 Pages: 148-155

    • DOI

      10.1186/s12866-021-02217-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insulin-like growth factor 1 promotes the extension of Tracheal Epithelium in an in Vitro Tracheal organ culture model2021

    • Author(s)
      Kishimoto Ippei、Ohnishi Hiroe、Yamahara Kohei、Nakagawa Takayuki、Yamashita Masaru、Omori Koichi、Yamamoto Norio
    • Journal Title

      Auris Nasus Larynx

      Volume: 48 Issue: 3 Pages: 441-450

    • DOI

      10.1016/j.anl.2020.09.017

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel method for live imaging of human airway cilia using wheat germ agglutinin2020

    • Author(s)
      Nakamura Ryosuke、Katsuno Tatsuya、Kishimoto Yo、Kaba Shinji、Yoshimatsu Masayoshi、Kitamura Morimasa、Suehiro Atsushi、Hiwatashi Nao、Yamashita Masaru、Tateya Ichiro、Omori Koichi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 14417-14417

    • DOI

      10.1038/s41598-020-71049-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term olfactory function outcomes after pituitary surgery by endoscopic endonasal transsphenoidal approach2020

    • Author(s)
      Kuwata Fumihiko、Kikuchi Masahiro、Ishikawa Masaaki、Tanji Masahiro、Sakamoto Tatsunori、Yamashita Masaru、Matsunaga Mami、Omori Koichi、Nakagawa Takayuki
    • Journal Title

      Auris Nasus Larynx

      Volume: 47 Issue: 2 Pages: 227-232

    • DOI

      10.1016/j.anl.2019.07.002

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recurrent laryngeal nerve regeneration using a self-assembling peptide hydrigel2020

    • Author(s)
      Yoshimatsu M, Nakamura R, Kishimoto Y, Yurie H, Hayashi Y, Kaba S, Ohnishi H, Yamashita M, Tateya I, Omori K
    • Journal Title

      Laryngoscope

      Volume: in press Pages: 100-102

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reversal of Vocal Fold Mucosal Fibrosis Using siRNA against the Collagen-Specific Chaperone Serpinh12019

    • Author(s)
      Kishimoto Yo、Yamashita Masaru、Wei Alice、Toya Yutaka、Ye Shuyun、Kendziorski Christina、Welham Nathan V.
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 16 Pages: 616-625

    • DOI

      10.1016/j.omtn.2019.04.014

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 気道再生医療の現状と展望2019

    • Author(s)
      山下 勝、大森 孝一
    • Journal Title

      分子呼吸器病

      Volume: 23(1) Pages: 18-20

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of multiciliated airway cells derived from human iPS cells using an artificial tracheal patch into rat trachea.2019

    • Author(s)
      Okuyama H, Ohnishi H, Nakamura R, Yamashita M, Kishimoto Y, Tateya I, Suehiro A, Gotoh S, Takezawa T, Nakamura T, Omori K
    • Journal Title

      J Tissue Eng Regen Med.

      Volume: Feb 26

    • DOI

      10.1002/term.2849

    • Related Report
      2018 Research-status Report
  • [Journal Article] Collagen sponge scaffolds containing growth factors for the functional regeneration of tracheal epithelium.2019

    • Author(s)
      Nakamura R, Katsuno T, Kitamura M, Yamashita M, Tsuji T, Suzuki R, Kishimoto Y, Suehiro A, Tateya I, Nakamura T, Omori K.
    • Journal Title

      J Tissue Eng Regen Med.

      Volume: Feb 26 Issue: 5 Pages: 835-845

    • DOI

      10.1002/term.2835

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alterations in macrophage polarization in injured murine vocal folds.2019

    • Author(s)
      Kaba S, Nakamura R, Yamashita M, Katsuno T, Suzuki R, Tateya I, Kishimoto Y, Omori K.
    • Journal Title

      Laryngoscope.

      Volume: 129(4) Issue: 4

    • DOI

      10.1002/lary.27523

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term preservation of planar cell polarity in reversed tracheal epithelium2018

    • Author(s)
      Tsuji Takuya、Nakamura Ryosuke、Katsuno Tatsuya、Kishimoto Yo、Suehiro Atsushi、Yamashita Masaru、Uozumi Ryuji、Nakamura Tatsuo、Tateya Ichiro、Omori Koichi
    • Journal Title

      Respiratory Research

      Volume: 19 Issue: 1 Pages: 22-22

    • DOI

      10.1186/s12931-018-0726-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis2017

    • Author(s)
      Suzuki Ryo、Katsuno Tatsuya、Kishimoto Yo、Nakamura Ryosuke、Mizuta Masanobu、Suehiro Atsushi、Yamashita Masaru、Nakamura Tatsuo、Tateya Ichiro、Omori Koichi
    • Journal Title

      The Laryngoscope

      Volume: 128 Issue: 4

    • DOI

      10.1002/lary.26959

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 耳鼻咽喉科疾患診療の最前線2022

    • Author(s)
      山下 勝
    • Organizer
      第84回 耳鼻咽喉科臨床学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Evidence-based Medicine in Logopedics and Phoniatrics2022

    • Author(s)
      Masaru Yamashita
    • Organizer
      第67回 日本音声言語医学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] コラーゲンビトリゲル膜を用いたヒトiPS細胞由来気道上皮細胞のラット鼻腔への移植2020

    • Author(s)
      桑田 文彦、山本 典生、林 泰之、北田 有史、山下 勝、小林 正佳、大森 孝一
    • Organizer
      第59回 日本鼻科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 精神遅滞者における舌下腺癌と考えられた一例2020

    • Author(s)
      山下 勝、高木 明
    • Organizer
      第30回 日本頭頸部外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 急速な増大を伴った弓部大動脈瘤による反回神経麻痺症例2019

    • Author(s)
      山下 勝、木谷 芳晴、倉田 馨介、音成 恵梨子、高木 明
    • Organizer
      第71回 日本気管食道科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 診断までに9ヶ月を要した特発性声門下狭窄の1例2019

    • Author(s)
      音成 恵梨子、木谷 芳晴、宮崎 和美、松原 彩、鳥居 紘子、山下 勝、高木 明
    • Organizer
      第116回 日本耳鼻咽喉科学会静岡県地方部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 頸部刺創の一例2019

    • Author(s)
      倉田 馨介、山下 勝、木谷 芳晴、鳥居 紘子、松原 彩、音成 恵梨子、高木 明
    • Organizer
      第117回 日本耳鼻咽喉科学会静岡県地方部会
    • Related Report
      2019 Research-status Report
  • [Presentation] MRIによる人工内耳磁石逸脱例2019

    • Author(s)
      松原 彩、高木 明、山下 勝、木谷 芳晴、鳥居 紘子、倉田 馨介、音成 恵梨子
    • Organizer
      第118回 日本耳鼻咽喉科学会静岡県地方部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 気道の再生2018

    • Author(s)
      山下 勝、楯谷 一郎、岸本 曜、末廣 篤、北村 守正、大森 孝一
    • Organizer
      日本呼吸器内視鏡学会 シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2024-01-30  

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