Characterisation of a primary ciliary dyskinesia model generated from BMI1-transduced basal epithelial cells.

Primary ciliary dyskinesia (PCD) is a rare genetic respiratory disorder, caused by a reduction in cilia number or dysmotility. Cilia dysmotility leads to breathing difficulties, concurrent infections and severe lung damage if not treated, with no therapies currently available. Improved airway epithelial cell models, that mimic the disease phenotype, are required for development of new therapeutics, as they exert limited potential of self-renewal in vitro. Here we describe a human PCD cell model by lentiviral transduction of airway basal epithelial cells with BMI1 gene, a regulator of senescence. We report that the cells retain their proliferation and differentiation capacity for at least 19 passages and recapitulate the disease phenotype with immotile cilia lacking DNAH5 and other outer dynein arm proteins. Characterisation of the ion transport properties of these PCD cells grown at air-liquid interface showed lower activity of the sodium channel ENaC and enhanced CFTR activity compared to non-PCD cells, which may be linked to ciliary immotility. Our study provides a robust PCD model for therapeutic studies and may open new avenues to investigate the molecular mechanisms of this disease.