Differentiated and functional human airway epithelium regeneration in tracheal xenografts

To investigate the regeneration process of a well-differentiated and functi onal human airway epithelium, we adapted an in vivo xenograft model in whic h adult human nasal epithelial cells adhere and progressively repopulate de nuded rat tracheae grafted in nude mice. The proliferating activity, the de gree of differentiation, and the barrier integrity of the repopulated epith elium were studied during the regeneration process at optical and ultrastru ctural levels with immunocytochemistry and a permeability tracer. Three day s after implantation in nude mice, tracheal xenografts were partially repop ulated with a flattened nonciliated and poorly differentiated leaky epithel ium. By the end of the first week after the graft, cell proliferation produ ced on the entire surface of the rat trachea an epithelium that was stratif ied into multiple layers and tightly sealed. During successive weeks, cell proliferation dramatically decreased. Moreover, the epithelium became progr essively columnar, secretory, ciliated, and transiently leaky. At 4-5 wk, a fully differentiated pseudostratified functional epithelial barrier imperm eable to a low-molecular-weight tracer was reconstituted. The regeneration of a well-differentiated and functional human airway epithelium in rat trac heae grafted in nude mice includes several steps that mimic the regeneratio n dynamics of airway epithelium after injury.