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 105 and 106 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.
|Titolo:||Engraftment of Bone Marrow-Derived Stem Cells to the Lung in a Model of Acute Respiratory Infection by Pseudomonas Aeruginosa|
COLOMBO, CARLA (Secondo)
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
|Data di pubblicazione:||lug-2009|
|Digital Object Identifier (DOI):||10.1038/mt.2009.96|
|Appare nelle tipologie:||01 - Articolo su periodico|