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The investigation of molecular mechanisms underlying refractory respiratory diseases using human lung derived organoids

利用人肺源性类器官研究难治性呼吸系统疾病的分子机制

基本信息

批准号：
22K19560
负责人：
新谷康
金额：
$ 4.16万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Research (Exploratory)
财政年份：
2022
资助国家：
日本
起止时间：
2022-06-30 至 2025-03-31
项目状态：
未结题

项目摘要

呼吸器領域では慢性閉塞性肺疾患（COPD）や特発性間質性肺炎など非可逆性の慢性進行性の肺疾患が急増しており、さらに新型コロナウイルスCOVID-19の後遺呼吸器障害による難治性呼吸器疾患に対する治療法の開発は重要な課題となる。少量のヒト由来組織を用いて、正常肺、COPD肺などの疾患由来組織によるオルガノイド作成技術を開発し、気道上皮肺オルガノイドを用いた難治性呼吸器疾患の病態解明、薬剤スクリーニング情報源としての役割評価および個別化医療を促進するバイオバンク構築を目的として本研究を計画した。まず、成人および小児正常肺よりオルガノイドを作成する技術を確立し、さらに継代できる培養条件を探索した。当科で肺切除を行った症例から、余剰肺組織を得てⅡ型肺胞上皮を抽出し3次元培養を開始してオルガノイドを樹立した。うち継代し得るものを選択し、各種実験に使用できることを確認した。今後、疾患肺よりオルガノイドを作成し、遺伝子・蛋白発現を解析し、疾患特異的な発現分子やシグナル伝達経路を探索する。さらに、１細胞RNAシークエンシング法により、オルガノイドに含まれる全ての細胞種と機能を評価する。成人正常肺由来オルガノイドと小児正常肺由来オルガノイド、正常肺由来オルガノイドと疾患肺オルガノイドを対比させることで、気道上皮肺の発生機序に重要な幹細胞群、疾患の病態に関連する細胞群を同定することを計画している。さらに正常肺由来オルガノイドを対照として、既存薬ライブラリーを使用し疾患由来オルガノイドの変化を観察することで、新たな創薬になりえる化合物を探索する予定である。

In the respiratory field, there is an important problem in the development of treatment methods for chronic pulmonary disease (COPD), idiopathic interstitial pneumonia, irreversible chronic progressive lung disease, and new types of respiratory disorders caused by COVID-19. This research project aims to develop new technologies for the development of pathologies, diagnosis and treatment of refractory respiratory diseases, information sources for service evaluation and promotion of individualized medical treatment in the development of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and use of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and use of pathology-based technologies for the development and use of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and use of pathology-based technologies for the development of pathology-based technologies for the development and development of pathology-based technologies for the development of To establish the technology for the production of normal lung tissue in adults and children, and to explore the culture conditions for the development of normal lung tissue in adults and children. When lung resection was performed, the remaining lung tissue was extracted from the type II lung epithelium, and the three-dimensional culture was started. All kinds of applications are confirmed. In the future, we will explore the development of disease-specific molecular pathways, the analysis of gene and protein expression, and the development of disease-specific molecular pathways. In addition, 1 cell RNA synthesis method is used to evaluate the function of all cell species. Adult normal lung origin, small normal lung origin, normal lung origin, disease origin The origin of normal lung disease is investigated by comparing it with the origin of existing lung disease, and the origin of new lung disease is investigated by exploring the origin of new lung disease.