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Primary Ciliary Dyskinesia patient specific hiPSC-derived airway epithelium in Air Liquid Interface culture recapitulates disease specific phenotypes in vitro

von Schledorn, L.; Martin, D. P.; Cleve, N.; Zoellner, J.; Roth, D.; Staar, B. O.; Hegermann, J.; Ringshausen, F.; Nawroth, J. C.; Martin, U.; Olmer, R.

2023-04-25 bioengineering
10.1101/2023.04.25.538316 bioRxiv
Show abstract

Primary ciliary dyskinesia (PCD) is a rare heterogenic genetic disorder associated with perturbed biogenesis or function of motile cilia. Motile cilia dysfunction results in diminished mucociliary clearance (MCC) of pathogens in the respiratory tract and chronic airway inflammation and infections successively causing progressive lung damage. Current approaches to treat PCD are symptomatic, only, indicating an urgent need for curative therapeutic options. Here, we developed an in vitro model for PCD based on human induced pluripotent stem cell (hiPSC)-derived airway epithelium in Air-Liquid-Interface cultures. Applying transmission electron microscopy, immunofluorescence staining, ciliary beat frequency and mucociliary transport measurements, we could demonstrate that ciliated respiratory epithelia cells derived from two PCD patient specific hiPSC lines carrying mutations in DNAH5 and NME5, respectively, recapitulate the respective diseased phenotype on a molecular, structural and functional level.

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