Therapeutic potential of murine bone marrow derived mesenchymal stem cells in influenza virus-induced pneumonia

Influenza virus (IV) infects the human upper respiratory tract and occasionally spreads to the alveolar compartment causing primary pneumonia. This can lead to acute respiratory distress syndrome (ARDS) with severe alveolar damage, lung oedema and hypoxemia. Antiviral therapies are only effective in the very beginning of infection and specific treatment strategies for IV-induced ARDS are lacking. Recent studies have shown the anti-inflammatory and regenerative potential of mesenchymal stem cells (MSC). MSC display a beneficial role in acute and chronic lung injury, suggesting that MSC delivery may be a promising treatment strategy in IV-induced ARDS [1].

We isolated MSC cells from the bone marrow of 8 to 12 weeks old C57Bl6 mice by cell sorting [2]. We characterised their expression markers by flow cytometry and we confirmed their differentiation potential into chondrocytes, osteocytes and adipocytes by microscopy. We co-cultured primary murine alveolar epithelial cells (AECs) with sorted MSC. During influenza infection with PR8 strain, the presence of MSC drastically reduced apoptosis and infection level in AECs. We tested the effect of MSC intratracheal instillation in PR8-infected mice. Similarly to the in vitro experiments, the addition of MSC improved clinical outcomes in comparison with PBS-instilled control mice.

Our experiments show the beneficial role of MSC in PR8-induced injury in vitro and in vivo. Taken together our results support that MSC can be of great value to treat IV-induced lung injury.

References:

Gupta N. et al. 2007.Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol,179(3):1855 – 1863.

Houlihan D.D. et al. 2012. Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-α. Nat protoc,7(12):2103 – 11.