P05 - Effects of long-term oxygen therapy on p53 dependent cellular crosstalk in idiopathic pulmonary fibrosis – studies in advanced organoid models
We study the beneficial and detrimental effects of short and long-term oxygen treatment in lung fibrosis while focussing on the mesenchymal-endothelial-epithelial crosstalk in a (reversible) p53-dependant manner. To study this, we will follow a stepwise approach to dissect the effects of LTOT on the gas exchange area of the fibrotic lung: We will i) characterize the dose-dependent effect of oxygen exposure in an advanced, i.e. vascularized human lung organoid (“lung on a chip”) to focus on cellular crosstalk mechanisms in time and spatial resolution under specific consideration of the effects on the “receiving” endothelium and the “operating” mesenchyme and epithelium. We will ii) characterize the specific role of fibrosis-characteristic immune cells in interaction with the endothelium and epithelium using a developed flow-chamber model. Cell specific analysis will include regulation of the oxidative stress response and DNA damage, thereby building on data of the previous funding period. In a treatment approach we will test the reversibility of the effects using pretreatment with, e.g. nintendani.