Fundamental research of the vocal cord regeneration using canine Adipose Derived Regenerative Cells (ADRCs)

• Project/Area Number: 15K10828
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Kurume University
• Principal Investigator: Umeno Hirohito 久留米大学, 医学部, 教授 (40203583)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2017: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2016: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 声帯再生 / 脂肪由来再生細胞 / 声帯上皮 / 声帯粘膜 / 声帯筋層 / 肝細胞増殖因子 / 吹鳴実験 / 病理組織学 / ヒアルロン酸 / 膠原線維 / 弾性線維 / 脂肪組織由来間葉系前駆細胞 / 声帯内自家脂肪注入術 / Celution®遠心分離機 / 血管内皮細胞 / 声帯内脂肪注入術 / 脂肪幹細胞 / 声帯外傷 / 声帯瘢痕 / 幹細胞増殖因子 / CD34 / CD90

Outline of Final Research Achievements

Canine Adipose Derived Regenerative Cells (ADRCs) combined with the autologous fat was injected into the canine vocal folds to prevent the post-operative fat absorption. At the side of ADRCs injection, larger fat graft area and more vascular endothelial cells were observed compared to the control side. ADRCs produced more hepatocyte growth factor (HGF) than normal fat tissue. HGF-producing ability of ADRCs was able to confirm by qPCR, but the multi-differentiation ability was not able to confirm by the induced differentiation. Good vocal fold vibration had seen with ADRCs injection group according to the blowing examination.
The pathological reproduction effect of the epithelium and muscular layer was not clear. However, hyaluronic acid production could confirm in lamina propria. The regenerate lamina propria thickened and detected that the sparse collagen fiber and hyperplasia of elastic fiber.

Academic Significance and Societal Importance of the Research Achievements

片側声帯麻痺や萎縮による嗄声や嚥下障害に対する声帯内自家脂肪注入術は、安全で有効な機能改善手術であるが、唯一の欠点は術後の自然な脂肪吸収による手術効果の減少である。本研究により、採取した脂肪由来再生細胞（ADRCs）を脂肪組織と混ぜて声帯に注入すると、手術効果を維持できる可能性が示唆された。
さらに、喉頭癌の声帯切除や外傷による声帯損傷に対する声帯の再生医療にADRCsを用いることで、声帯粘膜の再生が促される可能性が声帯吹鳴実験と病理組織学的評価によって示された。

Research Products

• [Journal Article] 一側声帯麻痺に対する声帯内注入術 (2015)
  • Author(s): 梅野博仁
  • Journal Title: 耳鼻咽喉科臨床 Volume: 108 Pages: 81-91
  • Open Access
• [Presentation] 脂肪細胞由来再生細胞（ADRCs）の声帯粘膜再生効果 (2020)
  • Author(s): 田中久一郎 梅野博仁 三橋亮太 佐藤文彦 岩畔英樹
  • Organizer: 第32回日本喉頭科学会
• [Presentation] Efficacy of ADRCs for autologous fat injection laryngoplasty (2019)
  • Author(s): Hisaichiro Tanaka, Hirohito Umeno, Ryota Mihashi, Fumihiko Sato, Shintaro Sueyoshi, Shun-ichi Chitose, Kiminori Sato
  • Organizer: The 99th Annual Meeting of the American Broncho-Esophagological Association
  • Int'l Joint Research
• [Presentation] 脂肪由来再生細胞(ADRCs)の声帯内脂肪注入術への効果 (2018)
  • Author(s): 田中久一郎、梅野博仁
  • Organizer: 第63回日本音声言語医学会
• [Funded Workshop] The 99th Annual Meeting of the American Broncho-Esophagological Association (2019)