Development of human alveolar organoid culture method using complete medium

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19491
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 53:Organ-based internal medicine and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Mitsuru Morimoto 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (70544344)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 肺胞オルガノイド / AT2細胞 / 肺線維症

Outline of Final Research Achievements

The aim of this study was to isolate alveolar stem cells from living human lung tissue and to develop a technique for the preparation of human alveolar organoids. By optimizing the previously reported medium for mouse alveolar organoids, a fully synthetic medium free of fibroblasts and serum was established, and human alveolar organoids were successfully prepared. In collaboration with Kobe University Hospital, fresh living human lung tissue was used to prepare alveolar organoids after isolation of AT2 cells. However, there is room for improvement as the spherical shape changes with passaging. This led to the establishment of an in vitro model of pulmonary fibrosis, a human respiratory disease, and the successful induction of adjacent myofibroblasts by DNA damage in AT2 cells.

Free Research Field

呼吸器幹細胞

Academic Significance and Societal Importance of the Research Achievements

ヒト肺胞オルガノイド培養の条件を確立できたこと、また肺線維症オルガノイド培養を確立できたことで、以下のような社会への貢献が期待できる。(1) 呼吸器疾患の研究と治療法開発: ヒト肺胞オルガノイドの作成技術を活用することで、呼吸器疾患の研究が促進される。(2) 新薬の開発と効果評価: ヒト肺胞オルガノイドを利用した新薬の効果評価や副作用の検討が可能となる。(3) 個別化医療の推進: 患者固有の肺疾患や治療反応を再現するin vitroモデルの構築により、個別化医療の実現が可能となる。患者に適した治療法の選択や治療効果の予測ができるようになるかもしれない。