Background/Aims: In Cystic Fibrosis (CF), the airway epithelium is progressively damaged and exhibits large areas of remodelling such as basal or goblet cell hyperplasia, ciliated cell absence or epithelial desquamation, therefore leading to mucociliary clearance impairment and loss of respiratory function. Using in vivo and in vitro models, we have previously demonstrated that the regeneration of CF airway epithelium is altered and leads to the reconstitution of a remodelled epithelium, even in absence of infection and inflammation. Experimental protocols of chronic inflammation in non-CF airway epithelial cells and inhibition of endogenous CF cell inflammation allowed us to assign a role for transient CF cell inflammatory memory in basal cell hyperplasia and in the increased height of CF airway epithelium, to highlight the involvement of lung tissue inflammation in goblet cell hyperplasia, the ciliated cell differentiation default being independent of inflammation. The identification of pharmacological compounds favouring mucociliary clearance through an improvement of CF airway epithelial regeneration is therefore crucial for patients with CF. In this perspective, we examined the influence of an agro-based compound (A-bC) obtained by bacterial fermentation of wheat, on the regeneration of the human CF airway epithelium. Methods: Airway epithelial cells obtained from nasal polyps from CF patients (F508del/F508del, n=3; F508del/W1282X, n=1) were cultured at the air-liquid interface for 35 days, in presence or not of A-bC and of Cytomix (TNF, IL1- and IFNcombo) in the basolateral medium. Epithelial regeneration was then investigated by counting the number of basal, ciliated and goblet cells, epithelium height was measured in culture sections, while IL-8 secretion was assessed by ELISA. Results: Measurements on haematoxylin/eosin-stained sections showed that A-bC decreased the CF airway epithelium height, even in presence of chronic inflammation. Quantification of immunofluorescence-detected CK13-positive and MUC-5AC-positive cells indicated a decrease in basal and goblet cell number, respectively, in A-bC-treated CF cultures, with no influence of Cytomix on this effect. The number of -tubulin-positive ciliated cells was significantly increased in CF cultures exposed to A-bC, which also reduced IL-8 secretion by CF cells. Conclusions: Our results show that A-bC avoids the inflammation-related CF airway epithelial remodelling, probably through the modulation of CF cell inflammatory phenotype. Moreover, A-bC improves the CF ciliated cell differentiation by a mechanism independent of its anti-inflammatory effect. These data allow us to propose A-bC as a pro-regenerative compound favouring key parameters for efficient mucociliary function in the CF airway epithelium. Acknowledgments: Vaincre La Mucoviscidose and Inserm.