Airway organoids are polarized 3D epithelial structures that mimic the organization and many of the major functions of the tissue in vivo. They represent an attractive model that can overcome some of the limitations of traditional 2D and air-liquid interface (ALI) models, but the limited accessibility of the apical side of the organoids prevents their application in studies focused on host-pathogen interactions. Here, a scalable, rapid, and efficient method for generating airway organoids in which the apical side is externally accessible was described. These apical-exposed airway organoids were generated from 2D-expanded bronchial epithelial cells in an environment devoid of extracellular matrix (ECM) and differentiated in suspension to develop organoid cultures of uniform size with robust cilia formation. Differentiated apical-aligned airway organoids were susceptible to infection with common respiratory viruses and showed variable responses to treatment with antiviral agents. In addition to the ease of access to the apical region, these apical-out airway organoids provide an alternative in vitro model for studying host-pathogen interactions with higher throughput than the conventional air-liquid interface model.
Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs
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