In patients with CRSwNP, the epithelium is damaged and shows an abnormal remodeling . As a consequence, the identification of molecular mechanisms of the upper airway epithelial cells involved in repair, proliferation, and mucociliary differentiation under normal and pathological conditions, offers some potential for the development of new strategies for CRSwNP treatment. A number of in vitro methods have been previously developed to investigate the nasal epithelium biology and physiopathology in human airways. The human nasal RPMI-2650 cell line, derived from squamous cell carcinoma of nasal septum, are widely used as an in vitro cell culture system due to are easily maintained in culture, has extended lifespan, improved proliferation and homogeneity, but they do not have the morphology, biochemical characteristics, and cellular response of control nasal epithelial cells. On the other hand, primary cells cultured in submerged culture, clearly undergo a dedifferentiation and loss of the original in vivo phenotype. An ideal human nasal epithelium in vitro model would require a morphologically well differentiated culture, with ciliated, non-ciliated, secretory, and basal cells, while showing epithelial function . These requirements are only present in the following in vitro culture systems: organotypic explant culture or primary cells cultured at the air-liquid interface. The former maintain the original epithelium whereas the latter mimic the epithelium. Organotypic explants are ex vivo models of nasal mucosa that can be cultured maintaining intact the original epithelium. In fact, they have been widely used to study the human normal and diseased nasal mucosa. However, due to presence of numerous cell types, matrices, and other environmental factors, explant culture models are less homogeneous, standarized, and reproducible than ALI culture models for primary epithelial cells. It is well-known that the ALI system provides a well differentiated culture that has been developed in both human upper and lower airways, as well as in different animals. Human nasal epithelial cells cultured in an ALI system represent the most promising experimental tool for investigating repair and differentiation, as well as to perform pharmacological, toxicological, and transport studies. Mucociliary differentiation in ALI culture models has been described with human nasal epithelial cells from inferior turbinates, and nasal polyps . Concerning to NP, studies from Bleier et al. and Hajj et al. described that it is possible to regenerate NP epithelium by culturing isolated epithelial or adult basal cells from NP at the ALI culture system, respectively. The former study demonstrated that NP their primary phenotype with respect to ciliary function and epithelial permeability, whereas the latter study provided evidence that restored epithelium was differentiated and showing intact immune barrier functions by secreting factors.
Reconstituted epithelium retained persistent symptomatic inflammation of the nasal and sinonasal mucosa
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