HIGH-THROUGHPUT SCREENING WITH PRIMARY HUMAN AIRWAY CELLS FOR REPURPOSING DRUGS TO PREVENT COVID-19

Purpose and goal

The goal of the project was to develop a novel 96 well-plate air-liquid interface based model of human airways using electrospun membranes. We developed this model using healthy and diseased primary human airway epithelial stem cells and developed techniques for live cell labeling and visualization of the model in real-time using high content imaging. We developed techniques for SARS-CoV-2 pseudovirus infection visualization with fluorescent reporters and optimized the platform for use with robotics for future high content imaging based drug screening.

Expected results and effects

We identified techniques for manufacturing electrospun membrane containing inserts for 96 well plates which could be subsequently coated with extracellular matrix proteins for formation of monolayers containing multicellular epithelium resembling human airways. We developed techniques to biologically characterize the cells grown on these membranes using genetic and histologic techniques to confirm we generated human airway-like structures. The project has resulted in a commercializable product which can be used for modeling human airways or drug screening.

Planned approach and implementation

The project was accomplished through collaboration between Cellevate AB, Lund University and Region Skåne. Cellevate AB and Lund University designed prototypes which were manufactured by Cellevate AB. Lund University optimized techniques for cell isolation (in collaboration with Region Skåne), cell seeding and techniques to assess the development of ´humanized airways´ in the inserts. Lund University developed techniques to infect and conduct drug screening in the new 96 well plate format. The results are being assembled for eventual publication.