Birchall, M. A. | bioRxiv Science

bioRxiv2020

Cell-intrinsic differences between human airway epithelial cells from children and adults

The airway epithelium is a key protective barrier, the integrity of which is preserved by the self-renewal and differentiation of basal stem cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic lung diseases, increasing age is a principle risk factor. Few studies have explored the differences between airway epithelial cells in children and adults and how the function of basal stem cells changes during ageing is poorly understood. Here, we analyze airway epithelial cells from children and adults in homeostatic conditions (laser capture-microdissected whole epithelium and fluorescence-activated cell-sorted basal cells) and in proliferation-inducing cell culture conditions. We find that, while the cellular composition of the pediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, pediatric airway epithelial cells displayed higher colony-forming ability, sustained in vitro growth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences between epithelium from children and adults, including higher baseline interferon-associated gene expression in pediatric epithelium. Our results demonstrate cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/027144v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@b7a680org.highwire.dtl.DTLVardef@1145543org.highwire.dtl.DTLVardef@1e9a86aorg.highwire.dtl.DTLVardef@12fe0bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

In vivo feasibility study of the use of porous polyhedral oligomeric silsesquioxane implants in partial laryngeal reconstruction.

BackgroundLoss of substantial volumes of laryngeal tissue after trauma or cancer significantly impairs quality of life. We hypothesised that repair of laryngeal defects with a candidate biomaterial, seeded with mesenchymal stem cells (MSC) and epithelial cells, may offer a therapeutic approach to this unmet need.\n\nMethodMoulded porous polyhedral oligomeric silsesquioxane polycarbonate-urea (POSS-PCU) scaffolds were seeded with human-derived MSC and epithelial cells, were implanted orthotopically into a defect created in the thyroid cartilage in eight pigs and monitored in vivo for 2 months. In vivo assessments were performed at 1, 2, 4 and 8 weeks post implantation. Histology was performed following termination.\n\nResultsImplant operations were uncomplicated. One pig was terminated early (2 weeks post-implantation) following expectoration of its implant. No other mortality or morbidity was observed. Endoscopy showed partial extrusion of implants at two weeks and complete extrusion of all implants by termination.\n\nConclusionsPOSS-PCU moulded laryngeal implants, in the present formulation, are extruded from the site of implantation between two- and eight-weeks post-surgery in pigs. In its present formulation and with the present, one-stage, protocol, this material does not appear to provide a suitable scaffold and vehicle for cells intended for partial laryngeal replacement in pigs.

bioengineering↗