| Popis: |
Idiopathic Pulmonary fibrosis (IPF) is an incurable chronic disease characterized by progressive loss of lung function. IPF is thought to occur due to repetitive micro injuries in the distal lung and/or genetic predisposition leading to aberrant tissue repair. Increased ECM deposition by myofibroblasts results in tissue stiffening and thickening of alveolar walls, causing progressive decline of pulmonary function and ultimately, fatal respiratory failure. Due to the inherent complexity of the human disease, advanced in vitro human models including physiological mechanical cues appear as a promising tool to investigate IPF and potential therapeutic interventions. We aimed to develop an advanced in vitro alveolar model mimicking some features of IPF. Primary alveolar epithelial cells and lung fibroblasts were co-cultured on the AlveoliX lung-chip-device and exposed to Transforming Growth Factor β (TGF-β), a central mediator of fibrogenesis. The effects on barrier disruption and gene expression of profibrotic markers were investigated. According to our results, fibroblasts supported alveolar barrier formation as detected by a faster development of barrier function and higher integrity. On the other hand, stimulation with TGF-s for 48h led to a decrease in barrier integrity over time, together with an increased expression of pro-fibrotic markers such as Col1a and Vimentin at the epithelial and fibroblast side. No significant effects on cytotoxicity or metabolic activity between treated and untreated wells were observed after 48h stimulation. In conclusion, our human in vitro model recapitulates some relevant features of IPF, hence, it may be a valuable tool for investigating new biomarkers and for efficacy studies of new antifibrotic drugs. |
