| Project/Area Number |
17K11313
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Yamagata University |
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Principal Investigator |
Ito Tsukasa 山形大学, 医学部, 准教授 (50344809)
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| Co-Investigator(Kenkyū-buntansha) |
窪田 俊憲 山形大学, 医学部, 講師 (80536954)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 中耳粘膜再生 / HMGB1 / 内視鏡下耳科手術 / 真珠腫性中耳炎 / 中耳真珠腫 / 中耳粘膜 / 線毛上皮 / モルモット / 再生医療 / 経外耳道的内視鏡下耳科手術 / 真珠製中耳炎 / 間葉系幹細胞 |
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| 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.
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| 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。
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