Extracellular Vesicles Derived from Mesenchymal Stromal Cells Reduce Pseudomonas aeruginosa Burden and the Inflammatory Response in Cystic Fibrosis Mouse Lung

Chronic lung infections and presistent inflammation are a leading cause of morbidity and mortality in people with cystic fibrosis and therefore there is a need for therapies that can simultaneously eliminate infection and the hyperinflammatory lung environment in CF. Mesenchymal stromal cell-derived extracellular vesicles (MSC EVs) represent a promising solution, offering potent anti-inflammatory, immunomodulatory, and antimicrobial properties while being safe and non-toxic. This study demonstrates the efficacy of MSC EVs in a CF mouse model of acute Pseudomonas aeruginosa lung infection. MSC EVs reduced Pseudomonas burden, immune cell infiltration, and pro-inflammatory cytokine levels in the lungs. MSCs were transfected with either 1) a mimic miRNA (negative control) with no known targets in P. aeruginosa or mice or 2) miRNA let-7b-5p. EVs were isolated from the MSCs and inoculated into the lungs of CF mice with an acute P. aeruginosa infection. These smRNA-seq data are from the MSC EVs and their parent MSCs.