Extracellular Vesicles Derived from Mesenchymal Stromal Cells Reduce Pseudomonas aeruginosa Lung Infection and Inflammation in Mice

The World Health Organization and the U.S. Centers for Disease Control and Prevention have reported that antibiotic resistant infections with Pseudomonas aeruginosa present a significant health risk world-wide. In the genetic disease Cystic Fibrosis (CF), chronic antibiotic resistant Pseudomonas lung infections and persistent inflammation remain the leading causes of morbidity and mortality. While highly effective modulator therapy (HEMT) dramatically improves lung function in CF, they fail to eradicate chronic infections or eliminate the associated hyperinflammatory state. Thus, there is an urgent need for innovative therapies that can simultaneously eliminate antibiotic resistant P. aeruginosa lung infection and the attendant hyperinflammatory lung environment. 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 using a CF mouse model of infection that MSC EVs reduce acute P. aeruginosa lung infection and inflammation. MSC EVs reduced Pseudomonas burden, immune cell infiltration, and pro-inflammatory cytokine levels. As the first investigation of MSC EVs in CF, this research underscores the dual effects of MSC EVs; mitigating inflammation and reducing bacterial burden. These findings mark an important advancement in antimicrobial therapy, addressing the unmet need for reducing antibiotic resistant infections and hyperinflammation for people with CF as well as the multitude of others with chronic, antibiotic resistant P. aeruginosa lung infections.