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Basic research for development of regenerative medicine for stiffened vocal folds according to severity

Research Project

Project/Area Number 19H03805
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Hirano Shigeru  京都府立医科大学, 医学(系)研究科(研究院), 教授 (10303827)

Co-Investigator(Kenkyū-buntansha) 椋代 茂之  京都府立医科大学, 医学(系)研究科(研究院), 助教 (00821860)
杉山 庸一郎  京都府立医科大学, 医学(系)研究科(研究院), 講師 (50629566)
斉藤 敦志  京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (80573633)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords声帯再生 / 声帯瘢痕 / 再生医療 / 幹細胞 / 細胞増殖因子 / PRP / 羊膜 / 細胞治療 / 増殖因子治療
Outline of Research at the Start

声帯が硬化し重度の音声障害をきたす声帯瘢痕、溝症には確立した治療法がなく、患者さんは長い病悩期間に苦しんでおり、早急の対応が必要である。我々は再生医療を駆使した先端的治療法開発のための研究を推進する。そのために、重症度別声帯瘢痕動物モデルの確立、病態に応じた声帯再生医療の指針の作成、軽度声帯瘢痕に対する治療戦略の構築、重度声帯瘢痕に対する治療戦略の構築、プラズマリッチ血小板(PRP)の声帯再生効果の検証、声帯粘膜の羊膜による全置換再生についての基礎実験を、臨床応用を目指して行う。これらの成果が声帯瘢痕で苦しむ患者さんの福音となることを期待している。

Outline of Final Research Achievements

Vocal fold scar causes severe dysphonia and remains difficult to treat. In order to overcome this, in vitro and in vivo animal experiments have been completed to develop novel regenerative treatments for vocal fold scar and sulcus. Growth factor (basic fibroblast growth factor, hepatocyte growth factor) or adipose derived mesenchymal stem cell have revealed to be effective for the regeneration in mild to moderate scar, while the effects were insufficient in severe scar. Plasma rich platelet or amniotic membrane turn out to be effective to regenerate such severe scar. The combination of growth factors or hybrid of growth factor and stem cell did not show significant additional regenerative effects. The research provided with possible ideal strategies for the treatment of vocal fold scar according to the severity of the disease.

Academic Significance and Societal Importance of the Research Achievements

声帯瘢痕は永続的で重度の音声障害をきたし、治療法が確立されていないがために、患者は長期に渡り病悩に苦しめられている。この解決のためには再生医療しか道はなく、世界的に多くの基礎研究が行われているものの、未だ決め手がないのが現状である。声帯瘢痕の重症度別の治療戦略が重要であり、今回の研究成果から軽度~中等度の瘢痕はほぼ解決でき、臨床応用の段階である。重度瘢痕について、本研究成果より効果的な治療法が見いだせる可能性がでてきた点、画期的な展開と考えている。さらなる研究により臨床応用に至れば苦しんでいる患者の福音となり、社会的意義は極めて大きいと考えられる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (27 results)

All 2023 2022 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results) Presentation (18 results) (of which Int'l Joint Research: 7 results,  Invited: 12 results)

  • [Journal Article] 声帯瘢痕・溝症に対する再生医療の現状と羊膜の応用.2022

    • Author(s)
      小川真智子、椋代茂之、中西庸介、吉崎智一、平野 滋.
    • Journal Title

      喉頭

      Volume: 34 Pages: 144-150

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tamoxifen Alters <scp>TGF</scp> ‐β1/Smad Signaling in Vocal Fold Injury2022

    • Author(s)
      Matsushita Hiroki、Mukudai Shigeyuki、Ozawa Satomi、Kinoshita Shota、Hashimoto Keiko、Kaneko Mami、Sugiyama Yoichiro、Branski Ryan C.、Hirano Shigeru
    • Journal Title

      The Laryngoscope

      Volume: - Issue: 9 Pages: 2248-2254

    • DOI

      10.1002/lary.30448

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Effects of Amniotic Membrane Transplantation on Vocal Fold Regeneration.2021

    • Author(s)
      Ogawa M, Mukudai S, Sugiyama Y, Matsushita H, Kinoshita S, Ozawa S, Hashimoto K, Fuse S, Kaneko M, Nakanishi Y, Yoshizaki T, Sotozono C, Hirano S
    • Journal Title

      Laryngoscope

      Volume: - Issue: 10 Pages: 2017-2025

    • DOI

      10.1002/lary.29997

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Repeated Intracordal Glucocorticoid Injection on the Histology and Gene Expression of Rat Vocal Folds.2021

    • Author(s)
      Hashimoto K, Kaneko M, Kinoshita S, Ozawa S, Mukudai S, Sugiyama Y, Hirano S. Effects of Repeated Intracordal Glucocorticoid Injection on the Histology and Gene Expression of Rat Vocal Folds. J Voice. 2021 Jul 17:S0892-1997(21)00199-5. doi: 10.1016/j.jvoice.2021.06.013. Online ahead of print.
    • Journal Title

      J Voice.

      Volume: E-pub

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-inflammatory and Antioxidant Effects of Japanese Herbal Medicine Kyoseihatekigan on Vocal Fold Wound Healing.2021

    • Author(s)
      Ozawa S, Mukudai S, Kaneko M, Kinoshita S, Hashimoto K, Sugiyama Y, Hashimoto S, Akaki J, Hirano S.
    • Journal Title

      J Voice

      Volume: E-pub

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physiological Effects of Voice Therapy for Aged Vocal Fold Atrophy Revealed by EMG Study.2021

    • Author(s)
      Kaneko M, Sugiyama Y, Fuse S, Mukudai S, Hirano S.
    • Journal Title

      J Voice.

      Volume: E-pub

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞増殖因子による声帯の再生医療up to date.2020

    • Author(s)
      平野 滋、杉山庸一郎、椋代茂之、橋本慶子、布施慎也、木下翔太、金子真美.
    • Journal Title

      日気食

      Volume: 71 Pages: 167-168

    • NAID

      130007835755

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms Underlying the Antifibrotic Potential of Estradiol for Vocal Fold Fibrosis2020

    • Author(s)
      Ozawa Satomi、Mukudai Shigeyuki、Sugiyama Yoichiro、Branski Ryan C.、Hirano Shigeru
    • Journal Title

      The Laryngoscope

      Volume: - Issue: 10 Pages: 2285-2291

    • DOI

      10.1002/lary.29355

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracordal Injection of Basic Fibroblast Growth Factor in 100 Cases of Vocal Fold Atrophy and Scar2020

    • Author(s)
      Hirano Shigeru、Sugiyama Yoichiro、Kaneko Mami、Mukudai Shigeyuki、Fuse Shinya、Hashimoto Keiko
    • Journal Title

      The Laryngoscope

      Volume: - Issue: 9 Pages: 2059-2064

    • DOI

      10.1002/lary.29200

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 日本のLaryngology-現在、過去、未来2023

    • Author(s)
      平野 滋
    • Organizer
      第35回日本喉頭科学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 喉頭科学の挑戦.再生医療の挑戦2023

    • Author(s)
      平野 滋
    • Organizer
      第32回日本頭頸部外科学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] The effects of amniotic membrane transplantation on vocal fold regeneration.2022

    • Author(s)
      Ogawa M, Mukudai S, Sugiyama Y, Yoshizaki T, Hirano S.
    • Organizer
      16th Meeting of International Association of Phonosurgery
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 声帯瘢痕の基礎と臨床-Scarwars.声帯瘢痕・溝に対する再生手術.2022

    • Author(s)
      杉山庸一郎、金子真美、平野 滋
    • Organizer
      第35回日本喉頭科学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 声帯瘢痕の基礎と臨床-Scarwars.羊膜移植の声帯再生における効果.2022

    • Author(s)
      小川真智子、椋代茂之、杉山庸一郎、中西庸介、吉崎智一、平野 滋
    • Organizer
      第35回日本喉頭科学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 美肌と美声と美脳を目指すアンチエイジング‐美声を維持するために.2022

    • Author(s)
      平野 滋
    • Organizer
      第22回日本抗加齢医学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Surgical treatment of vocal fold scar with or without growth factor.2021

    • Author(s)
      Hirano S
    • Organizer
      International Congress of ORL-HNS
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Surgical treatment of vocal fold scar.2021

    • Author(s)
      Hirano S
    • Organizer
      51st Brazilian Congress of Otorhinolaryngology and Facial Cervical Surgery
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Anti-inflammatory and Anti-oxidant Effects of Japanese Herbal Medicine Kyoseihatekigan On Vocal Fold Wound Healing2021

    • Author(s)
      Mukudai S, Ozawa S, Kaneko M, Sugiyama Y, Hirano S.
    • Organizer
      American Bronchoesophagological Association
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Videoexoscopic surgery of aerodigestive tract using 4K3D exoscopy.2021

    • Author(s)
      Hirano S, Sugiyama Y.
    • Organizer
      ORLIAC
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Estradiol Ameliorates Vocal Fold Fibrosis by Modulation of Estrogen Receptor-Mediated TGFb1 Signaling.2020

    • Author(s)
      Ozawa S, Mukudai S, Sugiyama Y, Branski R, Hirano S.
    • Organizer
      ALA meeting, 2020, May16-Jun 15, ePoster (Atlanta)
    • Related Report
      2020 Annual Research Report
  • [Presentation] Intracordal Injection of Basic Fibroblast Growth Factor into the Vocal Fold in 100 Cases of Atrophy, Scar or Sulcus.2020

    • Author(s)
      Hirano S, Sugiyama Y, Kaneko M.
    • Organizer
      ALA meeting, 2020, May16-Jun 15, ePoster (Atlanta)
    • Related Report
      2020 Annual Research Report
  • [Presentation] SMAD3抑制による声帯瘢痕治療におけるリピトイドの比較検討.2020

    • Author(s)
      椋代茂之、木下翔太、小澤聡美、布施慎也、橋本慶子、金子真美、杉山庸一郎、平野 滋.
    • Organizer
      第32回日本喉頭科学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] シンポジウム:喉頭における組織・機能再生の新展開.声帯瘢痕に対する肝細胞増殖因子を用いた再生医療:第I/II相医師主導治験.2019

    • Author(s)
      平野 滋
    • Organizer
      第31回日本喉頭科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 声帯線維芽細胞におけるグルココルチコイド受容体のリン酸化とTGFb/SMAD signalingへの関与.2019

    • Author(s)
      椋代茂之
    • Organizer
      第31回日本喉頭科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Histological findings in vocal folds.2019

    • Author(s)
      Hirano S.
    • Organizer
      21st International Workshop on Laser Voice Surgery, Paris,
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 声帯瘢痕に対する肝細胞増殖因子を用いた声帯再生医療:第I/II相医師主導治験.2019

    • Author(s)
      平野 滋.
    • Organizer
      第40回日本炎症・再生医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Panel: Regenerative medicine for vocal fold scar: phase I/II clinical trial of hepatocyte growth factor,2019

    • Author(s)
      Hirano S.
    • Organizer
      World Phonosurgery Congress, Buenos Aires
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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