Applications and research advancements of lung organoids in pulmonary diseases_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Qian ¹ , TAN Shiyan ¹ , WU Taoyu ¹ , MAO Zongyi ¹ , WANG Zifan ¹ , MA Qiong ^1,2 , ZHENG Chuan ^1,2 ,  REN Yifeng ^1,2 ,  YOU Fengming ^1,2

1. Oncology Teaching and Research Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, P. R. China;
2. TCM Prevention and Treatment of Metabolic and Chronic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, P. R. China;

Corresponding?author：

REN Yifeng, Email: ryftcm.dr@yahoo.com; YOU Fengming, Email: yfmdoc@163.com

Keywords：

Lung organoids; respiratory system; research model; clinical translation; disease model; review

DOI：

10.7507/1007-4848.202509007

Video：

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Abstract Full text Figures/Tables Video References Cited by

Pulmonary organoids currently represent the most accurate in vitro model for mimicking the structure and function of the human lung, serving as a transformative tool in respiratory research and medical practice. However, their broad application is hindered by several challenges, including limited maturity, lack of standardization, unclear regulatory pathways, high costs, and difficulties in scaling production. This review systematically outlines the current research status and development trends of pulmonary organoids, with emphasis on their value as in vitro models and research platforms for elucidating the biological features and pathophysiological mechanisms of lung diseases. Special attention is given to their emerging role in traditional Chinese medicine (TCM), such as evaluating pharmacological effects of herbal compounds, screening active ingredients, and exploring mechanisms underlying TCM syndrome differentiation and treatment. The aim of this review is to provide comprehensive evidence to support precision diagnosis, drug development, and therapeutic strategies for respiratory diseases.

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3. Barkauskas CE, Chung MI, Fioret B, et al. Lung organoids: current uses and future promise. Development, 2017, 144(6): 986-997.
4. Liberti DC, Morrisey EE. Organoid models: assessing lung cell fate decisions and disease responses. Trends Mol Med, 2021, 27(12): 1159-1174.
5. Sen C, Freund D, Gomperts BN. Three-dimensional models of the lung: past, present and future: a mini review. Biochem Soc Trans, 2022, 50(2): 1045-1056.
6. Schutgens F, Clevers H. Human organoids: tools for understanding biology and treating diseases. Annu Rev Pathol, 2020, 15: 211-234.
7. Ekanger CT, Zhou F, Bohan D, et al. Human organotypic airway and lung organoid cells of bronchiolar and alveolar differentiation are permissive to infection by influenza and SARS-CoV-2 respiratory virus. Front Cell Infect Microbiol, 2022, 12: 841447.
8. Alysandratos KD, Garcia-de-Alba C, Yao C, et al. Culture impact on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells. JCI Insight, 2023, 8(1): e158937.
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13. Dye BR, Hill DR, Ferguson MA, et al. In vitro generation of human pluripotent stem cell derived lung organoids. Elife, 2015, 4: e05098.
14. Porotto M, Ferren M, Chen YW, et al. Authentic modeling of human respiratory virus infection in human pluripotent stem cell-derived lung organoids. mBio, 2019, 10(3): e00723-19.
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17. Miao Y, Pek NM, Tan C, et al. Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids. Cell, 2025, 188(16): 4295-4313. e27.
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19. Kadur Lakshminarasimha Murthy P, Sontake V, Tata A, et al. Human distal lung maps and lineage hierarchies reveal a bipotent progenitor. Nature, 2022, 604(7904): 111-119.
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22. Dye BR, Youngblood RL, Oakes RS, et al. Human lung organoids develop into adult airway-like structures directed by physico-chemical biomaterial properties. Biomaterials, 2020, 234: 119757.
23. Clevers H. Modeling development and disease with organoids. Cell, 2016, 165(7): 1586-1597.
24. Beumer J, Geurts MH, Lamers MM, et al. A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses. Nat Commun, 2021, 12(1): 5498.
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