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Updated: Oct 27, 2025

Establishing Human Lung Organoids and Proximal Differentiation to Generate Mature Airway Organoids
Published on: March 23, 2022
Airway and Alveoli Organoids as Valuable Research Tools in COVID-19
Miriane de Oliveira1, Maria T De Sibio1, Felipe A S Costa2
1Department of Internal Clinic, Botucatu Medicine School, São Paulo State University (UNESP), District of Rubião Jr, s/n, 18618-000, Botucatu, São Paulo, Brazil.
Abstract:
The coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, SARS-CoV-2, affects tissues from different body systems but mostly the respiratory system, and the damage evoked in the lungs may occasionally result in severe respiratory complications and eventually lead to death. Studies of human respiratory infections have been limited by the scarcity of functional models that mimic in vivo physiology and pathophysiology. In the last decades, organoid models have emerged as potential research tools due to the possibility of reproducing in vivo tissue in culture. Despite being studied for over one year, there is still no effective treatment against COVID-19, and investigations using pulmonary tissue and possible therapeutics are still very limited. Thus, human lung organoids can provide robust support to simulate SARS-CoV-2 infection and replication and aid in a better understanding of their effects in human tissue. The present review describes methodological aspects of different protocols to develop airway and alveoli organoids, which have a promising perspective to further investigate COVID-19.
Insights
Human lung organoids offer a promising model for studying coronavirus disease 2019 (COVID-19) and its effects on respiratory tissues. This review details methods for developing these organoids to advance COVID-19 research and therapeutic development.
Area of Science:
- Biomedical research
- Infectious disease modeling
- Organoid technology
Background:
- Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, primarily impacts the respiratory system, leading to severe complications.
- Research on human respiratory infections is hindered by a lack of functional in vivo models.
- Organoid models offer a promising solution for replicating human tissue in vitro.
Purpose of the Study:
- To review methodological aspects of developing human airway and alveoli organoids.
- To highlight the potential of organoids in simulating SARS-CoV-2 infection and replication.
- To support the investigation of COVID-19's effects on lung tissue and aid therapeutic development.
Main Methods:
- Review of existing protocols for generating airway organoids.
- Review of existing protocols for generating alveoli organoids.
- Discussion of organoid culture techniques relevant to SARS-CoV-2 research.
Main Results:
- Organoid models can successfully mimic human lung physiology and pathophysiology.
- These models facilitate the study of SARS-CoV-2 infection and replication in human lung tissue.
- Organoids provide a platform for evaluating potential COVID-19 therapeutics.
Conclusions:
- Human lung organoids are valuable tools for understanding COVID-19 pathogenesis.
- Organoid technology offers a robust approach to overcome limitations in studying respiratory infections.
- Further development and application of organoid models are crucial for advancing COVID-19 research.

