Air-Liquid interface cultures to model drug delivery through the mucociliary epithelial barrier

Epithelial cells from mucociliary portions of the airways can be readily grown and expanded in vitro. When grown on a porous membrane at an air-liquid interface (ALI) the cells form a confluent, electrically resistive barrier separating the apical and basolateral compartments. ALI cultures replicate key morphological, molecular and functional features of the in vivo epithelium, including mucus secretion and mucociliary transport. Apical secretions contain secreted gel-forming mucins, shed cell-associated tethered mucins, and hundreds of additional molecules involved in host defense and homeostasis. The respiratory epithelial cell ALI model is a time-proven workhorse that has been employed in various studies elucidating the structure and function of the mucociliary apparatus and disease pathogenesis. It serves as a critical milestone test for small molecule and genetic therapies targeting airway diseases. To fully exploit the potential of this important tool, numerous technical variables must be thoughtfully considered and carefully executed.