Cystic fibrosis (CF) is one of the most frequent genetic
diseases,
caused by dysfunction of the CF transmembrane conductance regulator
(CFTR) chloride channel. CF particularly affects the epithelium of
the respiratory system. Therapies aim at rescuing CFTR defects in
the epithelium, but CF genetic heterogeneity hinders the finding of
a single and generally effective treatment. Therefore, in vitro models
have been developed to study CF and guide patient therapy. Here, we
show a CF model on-chip by coupling the feasibility of the human bronchial
epithelium differentiated in vitro at the air–liquid interface
and the innovation of microfluidics. We demonstrate that the dynamic
flow enhanced cilia distribution and increased mucus quantity, thus
promoting tissue differentiation in a short time. The microfluidic
devices highlighted differences between CF and non-CF epithelia, as
shown by electrophysiological measures, mucus quantity, viscosity,
and the analysis of ciliary beat frequency. The described model on-chip
may be a handy instrument for studying CF and setting up therapies.
As a proof of principle, we administrated the corrector VX-809 on-chip
and observed a decrease in mucus thickness and viscosity.