Targeted cell replacement with bone marrow cells for airway epithelial regeneration

1 Latner 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 2 Programme 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 Address for reprint requests and other correspondence: T. K. Waddell, Toronto General Hospital, 9N-949, 200 Elizabeth St., Toronto, Ontario, Canada M5G 2C4 (e-mail: tom.waddell{at}uhn.on.ca )