T4 Novel lung organoid model reveals crucial role of lung resident mesenchymal stromal cells in COPD pathogenesis

Abstract

T4 Figure 1Cellular condensation of primary distal lung cells;epithelial, endothelial, and mesenchymal stromal cells in Matrigel results in a large multicellular structure that matures over a period of 21 d to resemble the normal human alveoli. A Whole organoid imaging reveleas protruding bulbous structures projecting away from the main organoid body, are composed of SPC+ epithelial cells and are connected by a basic network of CD31+endothelial cells. Scale bar: 250 μm. Blue: DAPI, Green: SPC, Magenta: CD31. B Alveolar-like spheres are composed of SPC+ (green) and AQP5+ (red)cells. Scale bar: 100 μm. Blue: DAPI, Green: SPC, Red: AQP5. C Organoids formed with the seeding of MSCs isolated from healthy lungs (top) and MSCs isolated from lungs of COPD (bottom). Replacement of healthy MSCs with COPD MSCs results in loss of organoid symmetry and reduced size. Scale bar 1000 μm D HGF secretion levels are significantly lower in the organoids formed with COPD MSCs compared to organoids with healthy MSCs (P<0.05, Kurskal-Wallis)[Figure omitted. See PDF]ConclusionCondensation of primary pulmonary cells provides a physiologically relevant distal lung organoid model that features endothelial cell presence. COPD lung MSCs are not able to support growth of endothelial cells and induce irregular spatial organisation of alveolar epithelial cells.FundingMRC UK MR/S009426/1 to Dr. Anna KrasnodembskayaPlease refer to page A208 for declarations of interest related to this .