Targeted cell replacement with bone marrow cells for airway epithelial regeneration.
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.
Wong
Amy P
AP
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, Canada.
Dutly
Andre E
AE
Sacher
Adrian
A
Lee
Haeyul
H
Hwang
David M
DM
Liu
Mingyao
M
Keshavjee
Shaf
S
Hu
Jim
J
Waddell
Thomas K
TK
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016130:Immunophenotyping; D053538:Keratin-18 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D012137:Respiratory System / Q000166:cytology* / Q000473:pathology; D014132:Trachea / Q000166:cytology; D019076:Transgenes; D014598:Uteroglobin / Q000378:metabolism
D015415:Biomarkers; D053538:Keratin-18; D012333:RNA, Messenger; C556390:Scgb1a1 protein, mouse; D049452:Green Fluorescent Proteins; D014598:Uteroglobin