Stem cell therapy presents an attractive approach to cure cystic fibrosis (CF) lung disease. We set out to investigate the effect of epithelial damage caused by Pseudomonas aeruginosa, a pathogenic bacterium widely occurring in CF, on the engraftment of bone marrow cells in airway epithelium. Intravenous or intratracheal administration of unfractionated green fluorescent protein (GFP(+)) bone marrow cells in P. aeruginosa-infected mice resulted in none or very few GFP(+) cells detected in the lungs of the recipient mice, respectively. Only when GFP(+) bone marrow cells were purified to obtain a cell suspension enriched in progenitor cells and injected intratracheally, significant numbers of GFP(+) cells were detected. Localization of the donor cells at the level of airway epithelium was confirmed by Y-chromosome fluorescence in situ hybridization (FISH) analysis. All donor-derived Y-chromosome(+) cells were found to express cytokeratin (CK). The fractions of GFP(+) cells expressing CK were 0.34 and 0.76% for the 10(5) and 10(6) colony forming units (cfu) bacterial inoculums, respectively. When scored by Y-chromosome positivity these numbers were 0.60 and 1.12%, respectively. Our results show for the first time that tissue damage inflicted by bacteria like P. aeruginosa facilitates the airway engraftment of heterologous bone marrow-derived stem cells and their epithelial transformation.