Healthy and COPD iPSC derived lung organoids responds differently to SARS-CoV-2 infection - 08/04/25

iALI is a model of multiciliated airway epithelium derived from human induced pluripotent stem cells and generated in an air-liquid interface culture. This in vitro lung model was developed to study airway pathologies and infectious diseases such as SARS-CoV-2.

iALI were produced with iPSCs dedifferentiated from either healthy or patients with chronic obstructive pulmonary disease (COPD). SARS-CoV-2 infection of both iALI was validated by RTqPCR, infection plaque assays and immunofluorescence coupled to 3D super-resolution confocal microscopy. In addition, the innate immune response of infected and uninfected iALI was measured by RTqPCR and immunoassays.

We produced complete, functional bronchial epithelium; moreover, COPD iALI show hallmarks of the pathology: goblet cell metaplasia, basal cell hyperplasia and tissue inflammation. While both samples infect and replicate the virus for several weeks, with a peak 2 days after infection, viral production is limited in iALI COPD. Our results show expressions of interferon-stimulated genes (ISGs) and pro-inflammatory cytokines after infection with SARS-CoV-2 [1Assou S., Ahmed E., Morichon L., Nasri A., Foisset F., Bourdais C., y al. The transcriptome landscape of the in vitro human airway epithelium response to SARS-CoV-2 Int J Mol Sci 2023 ;  24 : 12017 [cross-ref]

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In conclusion, our results show that iALI can be used to study respiratory virus infection and its consequences on lung tissue, including from patients with COPD pathology.