Wong Amy P, Dutly Andre E, Sacher Adrian, Lee Haeyul, Hwang David M, Liu Mingyao, Keshavjee Shaf, Hu Jim, Waddell Thomas K
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.
Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L740-52. doi: 10.1152/ajplung.00050.2007. Epub 2007 Jul 6.
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.
有人提出，一些成年骨髓细胞（BMC）可定位于肺并发展出包括肺上皮细胞特征在内的组织特异性特征。在此，我们表明，作为引导BMC定位部位的预处理方案的轻度气道损伤（萘诱导）与短期培养的BMC经气管递送相结合，可增强气道定位并促使其呈现上皮样表型。用上皮标志物对气道和肺泡定位的BMC（荧光标记）进行共聚焦分析，结果显示肺上皮蛋白、克拉拉细胞分泌蛋白和表面活性物质蛋白C的表达。为了证实BMC的上皮基因表达，我们构建了由上皮特异性细胞角蛋白-18启动子驱动表达绿色荧光蛋白（GFP）的转基因小鼠，并在萘诱导气道损伤后，将来自这些小鼠的BMC经气管注射到野生型受体中。细胞递送后，在肺中观察到BMC至少留存120天，且随着时间的推移，GFP转基因表达增加。随着时间的推移，一些体外培养的BMC也表达GFP转基因，提示BMC发生了上皮转分化。结果表明，靶向递送BMC可促进气道再生。
