The therapeutic potential of the mesenchymal stem cell secretome in a mouse model of chronic inflammatory lung disease

Mesenchymal stem cells (MSCs) are spindle-shaped multipotent cells with immunomodulatory and reparative properties, which can be found in the mesenchymal stroma or connective tissues of the body. An ongoing pre-clinical study within our lab has found MSC-based therapy to significantly reduce inflammation and tissue damage in the lungs of Scnn1b-transgenic mice. These mice exhibit a chronic inflammatory lung disease due to airway-specific overexpression of the β-subunit of the epithelial sodium channel. Subsequently, we investigated whether administration of the MSC secretome, in a complementary cell-free approach, would exert similar effects. Scnn1b-transgenic mice were subcutaneously injected with control media or MSC-conditioned media (MSC-CM) every second day from birth to postnatal day 12, after which they were sacrificed at postnatal day 14. Analysis of the bronchoalveolar lavage fluid revealed significant reductions in both polymorphonuclear neutrophils and eosinophils in mice treated with MSC-CM. Histological analyses revealed that MSC-CM administration significantly improved two parameters of lung damage – the mean linear intercept and the destructive index. Overall, these results highlight the potential of the MSC secretome to limit lung damage and/or promote pulmonary repair/regeneration in the Scnn1b-transgenic mouse model of chronic lung disease.