Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Recent advances in lung organoid development and applications in disease modeling
Ana I. Vazquez-Armendariz, Purushothama Rao Tata
Ana I. Vazquez-Armendariz, Purushothama Rao Tata
Published November 15, 2023
Citation Information: J Clin Invest. 2023;133(22):e170500. https://doi.org/10.1172/JCI170500.
View: Text | PDF
Review Series

Recent advances in lung organoid development and applications in disease modeling

  • Text
  • PDF
Abstract

Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms derived from various sources, including adult, fetal, and induced pluripotent stem cells, have now been generated, which more closely mimic the cellular architecture found within the airways and alveoli. In this regard, the establishment of novel protocols with optimized stem cell isolation and culture conditions has given rise to an array of models able to study key cellular and molecular players involved in lung injury and repair. In addition, introduction of other nonepithelial cellular components, such as immune, mesenchymal, and endothelial cells, and employment of novel precision gene editing tools have further broadened the range of applications for these systems by providing a microenvironment and/or phenotype closer to the desired in vivo scenario. Thus, these developments in organoid technology have enhanced our ability to model various aspects of lung biology, including pathogenesis of diseases such as chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, and infectious disease and host-microbe interactions, in ways that are often difficult to undertake using only in vivo models. In this Review, we summarize the latest developments in lung organoid technology and their applicability for disease modeling and outline their strengths, drawbacks, and potential avenues for future development.

Authors

Ana I. Vazquez-Armendariz, Purushothama Rao Tata

×

Figure 1

Lung organoid models derived from adult mouse and human stem cells.

Options: View larger image (or click on image) Download as PowerPoint
Lung organoid models derived from adult mouse and human stem cells.
Seve...
Several epithelial progenitor/stem cells located along the bronchoalveolar compartment of murine and human lungs are capable of generating organoids. (A) Murine models include organoids derived from basal cells that form tracheospheres containing basal, ciliated, and secretory cells (10, 30). Club cells can be used to develop bronchiolospheres containing club and ciliated cells (38, 39). Coculture of BASCs with lung mesenchymal cells can give rise to bronchoalveolar lung organoids (BALOs) containing tubular-like structures with basal, club, goblet, and ciliated cells and saccular-like structures composed of differentiated AEC1s and AEC2s (26). When cocultured with lung endothelial cells, BASCs can form alveolar organoids, bronchiolar organoids, and bronchiolar organoids (41). Lastly, cocultures of AEC2s with PDGFRα+ mesenchymal cells lead to the formation of alveolospheres, containing AEC1s and AEC2s (13, 45, 47, 111). (B) Lung organoids derived from human adult stem cells can be generated from basal cells and AEC2s. Basal cells can form either tracheospheres or bronchospheres, depending on their location in the airways (10, 30–33). AEC2s form alveolar-like organoids when cocultured with feeder cells and display a similar composition to their mouse counterparts (13, 14, 50).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts