Establishment of functional 3D airway test systems for personalized approaches in rare airway diseases
23 April 2019 (online)
Primary ciliary dyskinesia (PCD) and Cystic fibrosis (CF) are rare diseases of the airways showing impaired mucociliary clearance due to different reasons. Several phenotypes exist in both, PCD and CF. Thus, different therapy strategies are required. Since 3D model organisms show a higher in vitro in vivo correlation than 2D cell culture, we aim to establish a functional 3D disease model in order to investigate patient-related therapies.
3D airway mucosa models were generated using decellularized porcine jejunal segments as scaffolds and human primary airway epithelial cells as well as fibroblasts for co-culture models. Mucociliary phenotype was verified by histological and ultrastructural analysis. For functional analysis ciliary beating frequency and particle transport studies were carried out. Therapeutical studies were performed using an aerosol exposure system.
The 3D models show a well-differentiated and polarized epithelium containing all important cell types (basal -, ciliated – and goblet cells) and mucus on the epithelial surface. Functionality of kinocilia is observed while cilia beat with a frequency of about 11 Hz in tracheal and about 13 Hz in nasal models. They show a mucociliary clearance velocity starting from 200 µm/s. Salbutamol or hypertonic sodium chloride could influence beat frequency.
We were able to successfully establish a personalized test system for respiratory epithelium. The 3D prototype enables to generate functional individual disease models and pre-therapeutic testing. This approach provides all requirements for personalized medicine in epithelial airway disorders.