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This Article Full Text Full Text (PDF) Supplemental Figures and Table All Versions of this Article: 293/3/L740    most recent 00050.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Wong, A. P. Articles by Waddell, T. K. Search for Related Content PubMed PubMed Citation Articles by Wong, A. P. Articles by Waddell, T. K.

Targeted cell replacement with bone marrow cells for airway epithelial regeneration

¹Latner Thoracic Surgery Research Laboratories, McEwen Centre for Regenerative Medicine, Toronto Lung Transplant Program, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto; and ²Programme in Lung Biology, Hospital for Sick Children, Toronto, Ontario, Canada

Submitted 2 February 2007 ; accepted in final form 2 July 2007

It has been suggested that some adult bone marrow cells (BMC) can localize to the lung and develop tissue-specific characteristics including those of pulmonary epithelial cells. Here, we show that the combination of mild airway injury (naphthalene-induced) as a conditioning regimen to direct the site of BMC localization and transtracheal delivery of short-term cultured BMC enhances airway localization and adoption of an epithelial-like phenotype. Confocal analysis of airway and alveolar-localized BMC (fluorescently labeled) with epithelial markers shows expression of the pulmonary epithelial proteins, Clara cell secretory protein, and surfactant protein C. To confirm epithelial gene expression by BMC, we generated transgenic mice expressing green fluorescent protein (GFP) driven by the epithelial-specific cytokeratin-18 promoter and injected BMC from these mice transtracheally into wild-type recipients after naphthalene-induced airway injury. BMC retention in the lung was observed for at least 120 days following cell delivery with increasing GFP transgene expression over time. Some BMC cultured in vitro over time also expressed GFP transgene, suggesting epithelial transdifferentiation of the BMC. The results indicate that targeted delivery of BMC can promote airway regeneration.

bone marrow cell; lung; epithelium; airway regeneration

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