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ドラッグデリバリーシステムを用いた細胞増殖因子による声帯萎縮の治療

Research Project

Project/Area Number 19659436
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Otorhinolaryngology
Research InstitutionKyoto University

Principal Investigator

平野 滋  Kyoto University, 医学研究科, 講師 (10303827)

Co-Investigator(Kenkyū-buntansha) 金丸 眞一  京都大学, 医学研究科, 講師 (30324643)
田村 芳寛  京都大学, 医学研究科, 助教 (40397550)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywords声帯萎縮 / 声帯瘢痕 / 再生医療 / 肝細胞増殖因子 / ドラッグデリバリーシステム / ゼラチンハイドロゲル / 声帯振動 / 組織再生 / 再生 / 喉頭 / 増殖因子 / 声帯 / 除放 / 瘢痕 / 細胞外マトリックス
Research Abstract

肝細胞増殖因子(HGF)を用いた声帯瘢痕の粘膜再生実験を行った。HGFにゼラチンハイドロゲルを付加することで、声帯粘膜内で2週間かけて除放するドラッグデリバリーシステムを構築した。これを用いてイヌ瘢痕声帯のin vivoにおける再生効果を検討した。イヌ声帯の一側を切除することで瘢痕を形成した。1ヶ月後および6ヵ月後の急性・慢性瘢痕に対し、それぞれHGFハイドロゲルを局所注射した。その効果を急性瘢痕においては6ヵ月後に、慢性瘢痕に対しては3ヵ月後に検討した。検討項目は摘出喉頭を用いた吹鳴実験による声帯粘膜の振動状態の定量化、ならびに喉頭の組織学的解析とした。(1)急性瘢痕に対する効果:吹鳴実験による声帯振動においては、HGF治療を行わなかった瘢痕声帯に対し、声帯振動の振幅の増大、声門閉鎖不全の改善、発声閾値声門下圧の有意な低下を認め、機能的な再生効果が認められた。組織学的検討においては、HGF治療群において、コラーゲンの蓄積の解消、ヒアルロン酸の回復、エラスチンの回復など、声帯の粘膜振動に必要な細胞外マトリックスの再構築が確認された。(2)慢性瘢痕に対する効果:慢性瘢痕にHGFを投与した群では、声門閉鎖不全は有意な改善は認められなかったが、声帯振動振幅の改善と発声閾値声門下圧の有意な低下を認め、急性瘢痕ほどではないが、粘膜の再生効果がえられた。組織学的にも、コラーゲンの過剰蓄積は解消され、ヒアルロン酸の回復が観察された。これらの結果は、HGFが急性瘢痕のみならず、治療が最も困難な慢性瘢痕においても、ある程度の粘膜再生効果を有することを示した。HGFを除放化することで、その効果がより強力にできた可能性が考えられた。

Report

(2 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (24 results)

All 2008 2007

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (17 results) Book (1 results)

  • [Journal Article] Effect of Hepatocyte Growth Factor on Gene Expression of Extracellular Matrix During Wound Healing of the Injured2008

    • Author(s)
      Ohno T, French LC, Hirano S, Ossoff RH, Rousseau B.
    • Journal Title

      Ann Otol Rhinol Laryngol. 117

      Pages: 696-702

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Extracellular Matrix Proteins in the Vocal Folds and Bone Marrow Derived Stromal Cells of Rats.2008

    • Author(s)
      Ohno T, Hirano S, Kanemaru S, Yamashita M, Umeda H, Suehiro A, Nakamura T, Ito J.
    • Journal Title

      Eur Arch Otorhinolaryngol. 2008 ; 265:669-674. 265

      Pages: 669-674

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regeneration of aged vocal fold : First human case treated with fibroblast growth factor.2008

    • Author(s)
      Hirano S, Yo Kishimoto, Atsushi Suehiro, Ken-ichi Kanemaru, Juichi Ito.
    • Journal Title

      Laryngoscope 118

      Pages: 2254-2259

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tracheal regeneration after partial resection: A tissue engineering approach.2007

    • Author(s)
      Yamashita M, Kanemaru S, Hirano S, et. al.
    • Journal Title

      Laryngoscope 117

      Pages: 497-502

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug delivery system of hepatocyte growth factor for the treatment of vocal fold scarring in a canine model.2007

    • Author(s)
      Ohno T, Hirano S, Kanemaru S, et. al.
    • Journal Title

      Ann Otol Rhinol Laryngol 116

      Pages: 762-769

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Side Population Cells in the Human Vocal Fold.2007

    • Author(s)
      Yamashita M, Hirano S, Kanemaru S, et. al.
    • Journal Title

      Ann Otol Rhinol Laryngol 116

      Pages: 853-857

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] Correction of posterior glottic gap for unilateral vocal fold paralysis using Gore-tex thyroplasty.2008

    • Author(s)
      Hirano S.
    • Organizer
      37th The Voice Foundation's annual symposium
    • Place of Presentation
      Philadelphia, U. S. A
    • Year and Date
      2008-06-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Histological structure of the vocal fold.2008

    • Author(s)
      Hirano S.
    • Organizer
      13th International Workshop on Laser voice surgery and voice care.
    • Place of Presentation
      Paris
    • Related Report
      2008 Annual Research Report
  • [Presentation] Cutting edge of healing process of the vocal cord in 2008.2008

    • Author(s)
      Hirano S.
    • Organizer
      13th International Workshop on Laser voice surgery and voice care.
    • Place of Presentation
      Paris
    • Related Report
      2008 Annual Research Report
  • [Presentation] Lasers in laryngology.2008

    • Author(s)
      Hirano S.
    • Organizer
      10th International symposium of phonosurgery
    • Place of Presentation
      Madison
    • Related Report
      2008 Annual Research Report
  • [Presentation] Roles of cells in the vocal fold and cell therapy.2008

    • Author(s)
      Hirano S.
    • Organizer
      6th International Conference on Voice Physiology and Biomechanics
    • Place of Presentation
      Tampere
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regeneration of aged vocal fold : First human case treated with fibroblast growth factor.2008

    • Author(s)
      Hirano S, Kishimoto Y, Suehiro A, Kanemaru S.
    • Organizer
      129th American Laryngological Association Meeting
    • Place of Presentation
      Orlando, U. S. A
    • Related Report
      2008 Annual Research Report
  • [Presentation] Use of basic fibroblast growth factor for atrophied vocal folds : Effects on cells, extracellular matrix, and2008

    • Author(s)
      Hirano S.
    • Organizer
      1st International Conference on Advances in Laryngeal Biophysiology
    • Place of Presentation
      Madison, U. S. A
    • Related Report
      2008 Annual Research Report
  • [Presentation] Anatomical and physiological bases of glottic vibration2007

    • Author(s)
      Hirano S
    • Organizer
      I Corso Teorico-Pratico di Lryngostroboscopia Diagnostica e Operativa
    • Place of Presentation
      Cesena, Italy
    • Year and Date
      2007-04-18
    • Related Report
      2007 Annual Research Report
  • [Presentation] Macula flava -role and ultra-structure-2007

    • Author(s)
      Hirano S
    • Organizer
      12th International Workshop on Laser voice surgery and voice care
    • Place of Presentation
      Paris
    • Related Report
      2007 Annual Research Report
  • [Presentation] Side population cells in the human vocal fold.2007

    • Author(s)
      Yamashita M, Hirano S, et. al.
    • Organizer
      128th American Laryngological Association
    • Place of Presentation
      San Diego
    • Related Report
      2007 Annual Research Report
  • [Presentation] Phonomicrosurgery for posterior glottic lesions using triangular laryngoscope.2007

    • Author(s)
      Hirano S, et. al.
    • Organizer
      128th American Laryngological Association
    • Place of Presentation
      San Diego
    • Related Report
      2007 Annual Research Report
  • [Presentation] Hepatocyte growth factor drug delivery system for the treatment of vocal fold scarring in a canine model.2007

    • Author(s)
      Ohno T, Hirano S, et. al.
    • Organizer
      87th American Bronchoesophagological Association
    • Place of Presentation
      San Diego
    • Related Report
      2007 Annual Research Report
  • [Presentation] The behavior of the autologous bone marrow derived stromal cells implanted in the vocal fold on healing2007

    • Author(s)
      Kanemaru S, Nakamura T, Yamashita M, Umeda H, Ohno T, Hirano S, Ito
    • Organizer
      87th American Bronchoesophagological Association
    • Place of Presentation
      San Diego
    • Related Report
      2007 Annual Research Report
  • [Presentation] Histologica deterioration of human scarred vocal folds after laser cordectomy.2007

    • Author(s)
      Hirano S, et. al.
    • Organizer
      36th The Voice Foundation's annual symposium
    • Place of Presentation
      Philadelphia, PA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Tissue engineering approaches for glottal regeneration: canine experiments.2007

    • Author(s)
      Yamashita M, Hirano S, Kanemaru S.
    • Organizer
      36th The Voice Foundation's annual symposium
    • Place of Presentation
      Philadelphia, PA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Vocal fold scarring and regeneration.2007

    • Author(s)
      Hirano S.
    • Organizer
      1st Shanghi International Voice Conference
    • Place of Presentation
      Shanghi
    • Related Report
      2007 Annual Research Report
  • [Presentation] Temporal chanage of vibratoy and acoustic functions of vocal fold scar after coredectomy.2007

    • Author(s)
      Kishimoto Y, Hirano S, Suehiro A, Kanemaru S.
    • Organizer
      1st Shanghi International Voice Conference
    • Place of Presentation
      Shanghi
    • Related Report
      2007 Annual Research Report
  • [Book] 発達期言語コミュニケーション障害の新しい視点と介入理論2007

    • Author(s)
      平野 滋
    • Total Pages
      317
    • Publisher
      医学書院
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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