Late Breaking Abstract - IPF lung-ECM subjected to cyclic stretch affect cellular activity

Abstract

Introduction: Idiopathic pulmonary fibrosis (IPF) involves extensive remodeling of the extracellular matrix (ECM), primarily in the periphery of the lung. This leads to altered mechanical properties, which in turn results in altered mechanical stimulation of the cells. In stiffer and less elastic ECM found in IPF, fibroblasts are thus exposed to altered strain compared to a healthy ECM. Our aim is to investigate the impact of mechanical stimulation on fibroblasts activity in IPF. Methods: IPF and healthy distal lung tissue were decellularized in slices (350 mm) to produce acellular lung scaffolds. The scaffolds were attached to a custom-made device for cyclic stretch built in polydimethylsiloxane and repopulated with healthy primary distal lung fibroblasts. The scaffolds were either exposed to cyclic stretch (0.2 Hz, 10% strain) or cultured under static conditions upto 3 days and analyzed for cell viability, histology, RNA expression, and released mediators. Results: Compared to healthy scaffolds, fibroblasts on IPF scaffolds showed increased metabolic activity, both at static and cyclic stretch condition. Scaffolds under cyclic stretch showed preserved tissue morphology with dispersed elongated fibroblasts shown with H&E staining. Interestingly, we see a shift in released mediators linked to angiogenesis in cyclic stretch cultures, mostly pronounced in IPF scaffolds. Discussion: We demonstrate that we have developed a physiological more relevant ex vivo model to study cellular responses in lung tissue. Our data indicate that there is a change in cellular activity in IPF tissue under cyclic stretch. This allows us to study the effect of alterations in mechanical and matrisome properties in chronic lung disease.