Extracellular Particles Derived From Mesenchymal Stromal Cells Reduce Pseudomonas aeruginosa Lung Infection and Inflammation in Mice

ABSTRACT The World Health Organization and the U.S. Centre for Disease Control and Prevention have reported that antibiotic‐resistant infections with Pseudomonas aeruginosa present a significant health risk worldwide. In the genetic disease Cystic Fibrosis (CF), chronic antibiotic‐resistant Pseudomonas lung infections and persistent inflammation remain the leading causes of 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 particles (MSC EPs) represent a promising solution, offering potent anti‐inflammatory and antimicrobial properties while being safe and non‐toxic. This study demonstrates, using a CF mouse model of infection, that MSC EPs reduce acute P. aeruginosa lung infection and inflammation. As the first investigation of MSC EPs in CF mice, this research underscores the dual effects of MSC EPs; reducing inflammation and bacterial burden. These findings mark an important advancement in antimicrobial therapy, addressing the unmet need for reducing antibiotic‐resistant infections and hyperinflammation in CF as well as other diseases with chronic, antibiotic‐resistant P. aeruginosa infections.