PMID- 19417738 OWN - NLM STAT- MEDLINE DCOM- 20091013 LR - 20211020 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 17 IP - 7 DP - 2009 Jul TI - Engraftment of bone marrow-derived stem cells to the lung in a model of acute respiratory infection by Pseudomonas aeruginosa. PG - 1257-65 LID - 10.1038/mt.2009.96 [doi] AB - 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. FAU - Rejman, Joanna AU - Rejman J AD - Institute for the Experimental Treatment of Cystic Fibrosis, H.S. Raffaele Scientific Institute, Milan, Italy. FAU - Colombo, Carla AU - Colombo C FAU - Conese, Massimo AU - Conese M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090505 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 SB - IM MH - Animals MH - Bone Marrow Cells/*cytology/*physiology MH - Bronchoalveolar Lavage Fluid/chemistry MH - Cell- and Tissue-Based Therapy/*methods MH - Lung/metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Pseudomonas Infections/*therapy MH - Pseudomonas aeruginosa/physiology MH - Respiratory Tract Infections/microbiology/*therapy MH - Stem Cells/cytology/physiology PMC - PMC2835203 EDAT- 2009/05/07 09:00 MHDA- 2009/10/14 06:00 PMCR- 2010/07/01 CRDT- 2009/05/07 09:00 PHST- 2009/05/07 09:00 [entrez] PHST- 2009/05/07 09:00 [pubmed] PHST- 2009/10/14 06:00 [medline] PHST- 2010/07/01 00:00 [pmc-release] AID - S1525-0016(16)31837-8 [pii] AID - 10.1038/mt.2009.96 [doi] PST - ppublish SO - Mol Ther. 2009 Jul;17(7):1257-65. doi: 10.1038/mt.2009.96. Epub 2009 May 5.