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Multi-dimensional Anti-Fibrotic Drug Screening Approaches in Human Lung Fibroblast Spheroids

Friday, 5 October 2018 at 16:30

Add to Calendar ▼2018-10-05 16:30:002018-10-05 17:30:00Europe/LondonMulti-dimensional Anti-Fibrotic Drug Screening Approaches in Human Lung Fibroblast Spheroids3D-Culture and Organoids in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com

Despite extensive efforts to develop effective in-vitro models for the study of lung diseases, there are still big challenges to fully recapitulate established in-vivo properties of lung cells. This study evaluates the mechanical properties of 3D spheroids from human airways smooth muscle cells (HASM) and parenchymal fibroblasts. Under low adhesion conditions, these mesenchymal cells form very regular spheroids with a uniform elastic exterior. These structures are assembled in the absence of added hydrogel through cell-cell adhesion to create a tissue-like structure with evenly distributed stress over the spheroid surface. We adapted micropipette aspiration to determine the elastic modulus using stepwise application of pressure to achieve a practical and rapid stiffness assay, which has never been explored in mesenchymal spheroids.   It shows excellent reliability and reproducibility and can be used to differentiate spheroids derived from patients with idiopathic pulmonary fibrosis, and evaluate their response to treatments. This mechanical characterization of spheroids represents a novel assay system for pre-clinical evaluation, when combined with biochemical, structural and pharmacological analyses. Using this approach, we demonstrated that casein kinase 1 delta inhibition has comparable or superior anti-fibrotic activity to the clinical agents, pirfenidone and nintedanib (Keenan et al, 2018).