Characterization of long-term cultured murine submandibular gland epithelial cells and tissue regeneration

Research Project

Project/Area Number	18K17238
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 57060:Surgical dentistry-related
Research Institution	Tokyo Metropolitan Komagome Hospital (Clinical research laboratory) (2019-2021) Keio University (2018)
Principal Investigator	Ikeura Kazuhiro 東京都立駒込病院(臨床研究室), 歯科口腔外科, 医員 (40784088)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	唾液腺再生 / 口腔乾燥 / 細胞株 / 分化誘導能 / 筋上皮細胞 / 腺房細胞 / 導管上皮基底細胞 / 唾液 / マウス顎下腺由来上皮細胞株 / 唾液腺組織再生 / 三次元培養 / 多分化能解析 / 唾液腺組織分泌機能評価のシステム構築
Outline of Final Research Achievements	Hyposalivation and xerostomia caused by aging or radiation therapy affect　the　patient’s QOL significantly. Therefore, the development of effective medical treatments is necessary. Until recently, tumor-derived or immortalized cell lines have been widely used in basic and preclinical research of salivary gland. However, these lines are pathophysiologically distinct from normal salivary gland tissue. And there weren’t any studies reported establishment of normal immortalized mouse salivary gland cell line. Salivary gland stem cells haven’t been isolated but it was supposed that proliferative cells are located around striated ducts or intercalated ducts. Accordingly, we tried differentiation induction into myoepithelial cells and acinar cells.
Academic Significance and Societal Importance of the Research Achievements	本研究の目的は、研究者が樹立した野生型マウス顎下腺由来培養上皮細胞株を用いた、唾液腺組織再構成の可能性について検証することである。唾液腺組織再生を目指した既報では腫瘍細胞由来・遺伝子改変動物由来の細胞株を用いた研究が主流だが、本研究ではマウスにおける自然発生的な細胞株を樹立し、その特性解析と腺組織を構成する細胞群への分化誘導能の検証を行ったことに学術的意義がある。将来的には樹立した安全かつ安定供給が可能な培養細胞株を用いて、腺組織の分泌機能評価が行えるシステムの開発を考えており、口腔乾燥症治療における新たな薬剤のスクリーニングに応用することで実際の臨床へのフィードバックが期待できる。