An HTS-Compatible Plate For Highly Miniaturized Cultures Of Primary Human Bronchial Epithelial Cells At Air-Liquid Interface

An obstacle to use of HBE-ALI models for high throughput screening (HTS) has been the severely limited supply of tissue samples from patients with unusual CFTR mutations. We have developed a plate for highly miniaturized, arrayed HBE-ALI cultures suitable for use in automated drug screening and mechanistic studies (μALI Plate). Cells cultured on the μALI Plate exhibit hallmarks of HBE biology including beating cilia and mucus production, but require less than one tenth the number of cells compared to conventional Transwell filters. Cells grown in this manner can be visualized directly from the apical surface by immunohistochemistry without the requirement to image through a filter support. Primary cells grown on the μALI Plate will be useful for testing therapeutic interventions directed towards patients with uncommon CFTR variants. Studies of ion channel function, cilia beat frequency and airway surface liquid depth are currently underway. Among other things, the μALI technology has the potential to facilitate personalized approaches to CF therapy, including drug development.