Abstract
Translation of novel inhalable therapies for respiratory diseases is hampered due to the lack of representative in vitro cell models. More advanced in vitro models that better recapitulate the extracellular matrix of the lungs have the potential to improve the translation of novel inhaled therapies by more accurately reflecting in vivo respiratory pharmacological and toxicological responses.
Herein, tissue-engineered collagen hyaluronic acid bilayered scaffolds (CHyA-B) (3D) were used to evaluate bacterial (Lipopolysaccharide (LPS)) and drug (bleomycin) induced toxicity and inflammation in Calu-3 bronchial epithelial cells and Wi38 lung fibroblasts co-cultures and compared to the responses seen in these cells co-cultured on the more standard Transwell® inserts (2D).
Differential responses to challenges were seen between the Calu-3:Wi38 co-cultures grown in 2D and 3D. Co-cultures exposed to LPS (10 µg/ml) showed higher IL-8 secretion (3100±843 pg/ml in 2D and 6464±5274 pg/ml in 3D) when grown in 3D compared to 2D. Co-cultures exposed to bleomycin (100 µg/ml) in 3D had a decreased cell metabolic activity (89±14% in 2D and 60±15% in 3D) relative to untreated samples in comparison to 2D treated co-cultures. LPS and bleomycin were further employed as controls to evaluate epithelial cell responses following novel inhalable nanotherapies in 3D and 2D.
Epithelial co-cultures grown in an extracellular matrix like environment show distinct epithelial responses in cytokine release and metabolic activity compared to 2D polarised models which can better mimic in vivo responses to toxic and inflammatory stimuli offering an innovative in vitro platform for respiratory drug development.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2043.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021