Healthy and COPD iPSC derived lung organoids responds differently to SARS-CoV-2 infection

Abstract

Introduction

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.

Methods

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.

Results

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 [1] and at a higher level in iALI with COPD.

Conclusion

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.