Establishment of an olfactory epithelia regeneration model to elucidate the mechanism of olfactory epithelial regeneration and to validate drug effects

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16840
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Kyoto University
• Principal Investigator: Masaaki Ishikawa 京都大学, 医学研究科, 客員研究員 (10813743)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 嗅上皮 / 嗅神経 / 層構造 / 軸索伸長 / OMP / 組織培養

Outline of Final Research Achievements

The purpose of this study was to establish a long-term culture method of olfactory epithelial tissue that retains its three-layer structure as a research model for elucidating the mechanism of olfactory regeneration and developing a regeneration method. First, we established the conditions for the detection of supporting cells, olfactory nerve, and basal cells, which constitute the olfactory epithelium, by fluorescence immunostaining. Next, we introduced OMP-GFP mice, which express GFP under the promoter of olfactory nerve marker protein OMP. Then the nasal septum of newborn mice of ICR mice and OMP mice were used for examination of conditions for olfactory epithelial tissue culture. As a result, we confirmed the conditions under which olfactory neurons die and basal cells which is tissue stem cells survive, by this result, an olfactory nerve physical damaged model was established.

Free Research Field

耳鼻咽喉科・頭頸部外科

Academic Significance and Societal Importance of the Research Achievements

嗅覚の再生機序の解明と再生促進のための研究モデルとして、マウスなどの実験動物と嗅上皮初代培養が用いられているが、前者では継時的観察や嗅神経から嗅球への軸索伸長とシナプス形成に関する検討が難しく、後者は生体の組織構築を反映していないという不備がある。そこで本研究では、生体で見られる複数の細胞種による3層構造を保持した状態の嗅上皮組織を長期間培養できる培養法を検討し、薬剤処理などによる障害からの再生過程を詳細かつ継時的に観察できる培養系の検討を試み、物理的損傷モデルを確立した。本モデルを用いることで層構造再生に必要な因子の探索が可能であり、嗅上皮再生治療薬の探索に貢献できる可能性がある。