Engraftment of bone marrow-derived stem cells to the lung in a model of acute respiratory infection by Pseudomonas aeruginosa.
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.
Institute for the Experimental Treatment of Cystic Fibrosis, H.S. Raffaele Scientific Institute, Milan, Italy.
Joanna
J
Rejman
Carla
C
Colombo
Massimo
M
Conese
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000628:therapy*; D011550:Pseudomonas aeruginosa / Q000502:physiology; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000628:therapy*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology