Developing alveolar organoid recapitulating injury-regeneration-imflammation-fibrosis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22630
• 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: Morimoto Mitsuru 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): 2019-06-28 – 2021-03-31
• Keywords: 肺胞オルガノイド / 肺線維症

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis (IPF) is a disease in which alveolar fibroblasts become myofibroblast, reducing the efficiency of gas exchange. There is a need for an experimental system that could reproduce IPF in vitro. We modulated the three-dimensional culture method of alveolar epithelial cells, known as alveolar organoid culture method. Using this culture system, we attempted to develop an experimental system reproducing the process of injury-regeneration-fibrosis induction in vitro that occurs in IPF in vivo. We succeeded in expressing fibrosis-inducing factors such as Tgfb1 into alveolar epithelial cells via drug-induced damage. Furthermore, incubation of lung fibroblasts with culture supernatant of the drug-damaged epithelial cells transformed to myofibroblasts.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

IPFは加齢に伴って増加する疾患であり、超高齢化社会を迎える日本において今後より患者数が増加していと予想される。肺の繊維化は上皮の損傷-再生の慢性化に起因すると考えられ、そのプロセスは肺胞上皮細胞の障害に始まる。本研究で開発しているin vitroの肺線維症モデルが完成すれば、これまで行えなかった発症プロセスの検証や、将来的に予防薬の新規ターゲットの探索や化合物スクリーニングへの応用も考えられる。