Cellular Dynamics of Tympanic Membrane and Identification of tympanic membrane tissue stem cells

Research Project

Project/Area Number	16K20287
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Otorhinolaryngology
Research Institution	The Tazuke Kofukai
Principal Investigator	Rie Kanai 公益財団法人田附興風会, 医学研究所神経・感覚運動器研究部, 主任研究員 (30574008)
Project Period (FY)	2016-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	tympanic membrane / tissue stem cell / identification / cellular dynamics / 鼓膜穿孔閉鎖過程 / 固有層 / 上皮層 / 膠原繊維 / Ki67陽性細胞 / 鼓膜 / 穿孔閉鎖過程 / 中間層 / Ki ６７陽性細胞 / 鼓膜穿孔 / 閉鎖過程 / 前駆細胞 / 免疫染色 / 組織幹細胞 / マウス鼓膜 / EdU / ビメンチン / サイトケラチン / 鼓膜穿孔モデル / ３層構造 / 鼓膜輪 / ツチ骨柄および臍部
Outline of Final Research Achievements	Tympanic membrane perforations (TMP) were created in C57/BL6 mice and sacrificed over time (Day 0, 1, 5, 10, 15, 20), and middle ear tissues were evaluated immunohistochemically. Early in the process of TMP closure, Ki67-positive cells, suggestive of progenitor cells, appeared at the annulus side of the epithelial layer, and the entire epithelial layer was proliferating. In the middle stage of closure, Ki67-positive cells appeared at the perforation edge side of the lamina propria, and fibroblast was proliferating especially on that site. Although we could not identify tissue stem cells of TMP, we found that the cellular dynamics during the closure process differed between the epithelial layer and the lamina propria.
Academic Significance and Societal Importance of the Research Achievements	鼓膜の組織幹細胞の同定にはいたらなかったが、穿孔が閉鎖する過程における上皮層と固有層の細胞動態、ならびに両者の差異が明らかになった。このことは鼓膜穿孔が残存するメカニズムの解明や、鼓膜穿孔閉鎖治療の開発において有用な情報になりうると考えられる。