Study for the curative treatment of middle ear cholesteatoma by regeneration of middle ear mucosa using autologous stem cell induction

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11313
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Yamagata University
• Principal Investigator: Ito Tsukasa 山形大学, 医学部, 准教授 (50344809)
• Co-Investigator(Kenkyū-buntansha): 窪田 俊憲 山形大学, 医学部, 講師 (80536954)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 中耳粘膜再生 / HMGB1 / 内視鏡下耳科手術 / 真珠腫性中耳炎

Outline of Final Research Achievements

A model of middle ear mucosal damage was established using guinea pigs. Via transcanal approach using a 1.9 mm rigid endoscope under general anesthesia, the middle ear mucosa in the ciliated epithelial region around the Eustachian tube was scraped after opening the anterior tympanic membrane. Histological evaluation of the mucosal damage site by HE staining at 2 weeks postoperatively showed that the ciliated epithelial cells had disappeared and the normal mucosa had not regenerated in the mucosal damage model.
We attempted to regenerate the mucosa of the middle ear by topically administering high-mobility group box 1 (HMGB1), a molecule that acts in tissue repair through induction of autologous bone marrow mesenchymal stromal cells, but found increased abnormal granulation tissue and submucosal bone thickening at the site of mucosal damage, suggesting that HMGB1 rather promotes an inflammatory response.

Free Research Field

耳鼻咽喉科頭頸部外科

Academic Significance and Societal Importance of the Research Achievements

中耳粘膜再生の研究を進めることにより、耳科手術後の中耳粘膜再生治療が可能となれば、これまで予防困難であった真珠腫再形成再発を比較的簡便な方法で制御できるとともに、術後聴力成績の向上も期待され、中耳炎症例のQOLにも貢献できる。本研究では内視鏡下経外耳道操作による低侵襲な方法で、HMGB1局所投与による内在性骨髄間葉系間細胞（MSC)誘導を介した中耳粘膜再生を試みたが、結果としては逆に障害後の炎症を促進させるものであった。現在、HMGB1に代わる薬剤として、鼻粘膜での線毛上皮細胞の回復効果が報告されているレチノイドを用いた中耳粘膜再生のための研究を開始している。