Mesenchymal stem cell therapy in a model of chronic inflammatory lung disease

Mesenchymal stem cells (MSCs) are multipotent stromal cells that have been investigated in a number of lung diseases due to their immunomodulatory and reparative potential. In this study, we investigated whether MSC administration could reduce inflammation and tissue damage in the lungs of transgenic mice (scnn1b-Tg) overexpressing the β-subunit of the epithelial Na(+) channel (β-ENaC). At 8 weeks of age, the lungs of scnn1b-Tg mice are characterised by chronic lung inflammation, structural tissue damage and a reduction in lung function. To test whether MSC therapy could alter this phenotype, we administered PBS (vehicle control) or MSC cells (5 x 105 cells in 100 μl PBS) through tail vein injection at 4 and 6 weeks of age, with the endpoint at 8 weeks. Broncholaveolar lavage fluid analysis revealed that MSC administration significantly reduced infiltration of inflammatory cells into the lungs as total cell counts, monocytic cells and neutrophil counts were significantly decreased. Tissue analysis revealed that the mean linear intercept (MLI) and destructive index (DI), both markers of emphysema, were significantly improved in MSC treated mice. These findings were confirmed using lung function analysis on the SciReq Flexivent, which revealed that lung damage was significantly reduced after MSC therapy. In addition, analysis of gene expression profiles from macrophages extracted from MSC treated mice revealed a number of potential mechanisms of action, which are currently under investigation. These data suggest that MSC therapy can reduce inflammation and damage and that MSCs may provide an effective tool in the treatment of chronic inflammatory lung disease.