Reconstituted basement membrane enables airway epithelium modeling and nanoparticle toxicity testing
Résumé
Basement membrane (BM) acts as a sheet-like extracellular matrix to support and promote the formation of epithelial and endothelial cell layers. The in-vitro reconstruction of the BM is however not easy due to its ultrathin membrane features. This difficult is overcome by self-assembling type IV collagen and laminin in the porous areas of a monolayer of crosslinked gelatin nanofibers deposited on a honeycomb microframe. Herein, a method is presented to generate airway epithelium by using such an artificial basement membrane (ABM) and human-induced pluripotent stem cells (hiPSCs). Bipolar primordial lung progenitors are firstly induced from hiPSCs and then replated on the ABM for differentiation toward matured airway epithelium under submerged and air-liquid interface culture conditions. As result, a pseudostratified airway epithelium consisting of several cell types is achieved, showing remarkable apical secretion of MUC5AC proteins and clear advantages over other types of substrates. As a proof of concept, the derived epithelium is used for toxicity test of cadmium telluride (CdTe) nanoparticles (NPs), demonstrating the applicability of ABM-based assays involving hiPSC-derived epithelial cells. based assays.
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