Regeneration for vocal fold sulcus with amniotic membrane

• Project/Area Number: 19K22691
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyoto 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), 助教 (50629566)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 声帯再生 / 再生医療 / 声帯瘢痕 / 間葉系幹細胞 / 線維芽細胞 / 分化誘導 / 羊膜 / 細胞治療 / 増殖因子治療 / 声帯溝症

Outline of Research at the Start

声帯溝症を想定した声帯粘膜の羊膜による全置換技術の開発を目的とし、動物を用いた声帯への羊膜移植実験とその基礎的実験を行う。ラット、ラビット、もしくはイヌを用いて喉頭截開後に声帯粘膜と羊膜の全置換を行い、組織学的な再生効果を検討するとともに、各種細胞外マトリックスや細胞増殖因子の遺伝子発現を確認する。また羊膜と声帯線維芽細胞との親和性や、羊膜と線維芽細胞増殖因子、肝細胞増殖因子との相乗効果について検討する。これらの成果をもとに羊膜移植を用いた再生医療のヒトへの応用へとつなげたい。

Outline of Final Research Achievements

Vocal fold scar remains problematic. Particularly severe scar is still difficult to treat even with regenerative methods. We examined the effects of the amniotic membrane for regeneration of the whole vocal fold mucosa using rat and rabbits. Rat vocal fold fibroblasts were seeded on amniotic membrane in culture medium, and appropriate survival and proliferation were observed. Then the amniotic membrane was transplanted to the rabbit vocal folds. Regeneration of the vocal folds were observed at 1 month after the implant. The histology showed good deposition of hyaluronic acid in the lamina propria of the vocal folds. The results indicate the feasibility of the amniotic membrane for vocal fold regeneration.

Academic Significance and Societal Importance of the Research Achievements

重度の声帯瘢痕や声帯溝症に対する革新的な治療法の開発に向け、羊膜が科学的に有用であることを証明した。これらの疾患に苦しむ患者さんへの臨床応用が期待できる。

Research Products

• [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
  • Peer Reviewed
• [Journal Article] Intracordal Injection of Basic Fibroblast Growth Factor in 100 Cases of Vocal Fold Atrophy and Scar (2020)
  • 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
  • Peer Reviewed
• [Presentation] 声帯粘膜再生における羊膜移植の効果． (2022)
  • Author(s): 小川真智子、椋代茂之、杉山庸一郎、松下大樹、木下翔太、小澤聡美、橋本慶子、布施慎也、金子真美、平野 滋．
  • Organizer: 第34回日本喉頭科学会
• [Presentation] The effects of human amniotic membrane transplantation for vocal fold regeneration. (2021)
  • Author(s): Ogawa M, Mukudai S, Matsushita H, Kinoshita S, Ozawa S, Hashimoto K, Kaneko M, Nakanishi Y, Sugiyama Y, Yoshikazu T, Hirano S.
  • Organizer: European Laryngoglocial Association,
  • Int'l Joint Research