We have used mesenchymal stem cells in preclinical models of pulmonary hypertension (PH) and in the hyperoxia-induced neonatal murine model of bronchopulmonary dysplasia (BPD) to suppress inflammation and improve survival while attenuating alveolar injury and PH. The protective effect was predominantly mediated by paracrine mechanisms, since, cell-free MSC-conditioned media were even more efficacious than MSCs in preventing or reversing established disease. The active moieties that confer the therapeutic efficacy of MSCs remain elusive but likely include secreted proteins, nucleic acids, and membrane components, all potentially packaged in MSC-released microvesicles. We have shown that such particles, a class of which is represented by exosomes, convey the therapeutic efficacy of MSCs in the murine hypoxic model of PH. Exosome treatment was also able to abrogate early hypoxic macrophage influx and downregulate hypoxia-activated inflammatory pathways, thus recapitulating the well-characterised, anti-inflammatory properties of MSCs. The clinical use of MSCs in several on-going trials or the MSC secretome (e.g. exosomes) is a budding new field that represents an exciting and promising approach to therapeutic interventions for diseases of the lung.
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