Sharanya Sarkar, Roxanna Barnaby, Amanda B Nymon, Lily A Charpentier, Lily Taub, Matthew J Wargo, Daniel J Weiss, Tracey L Bonfield, Bruce A Stanton
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引用次数: 0
Abstract
Cystic Fibrosis (CF) is a multiorgan disease caused by mutations in the CFTR gene, leading to chronic pulmonary infections and hyperinflammation. Among pathogens colonizing the CF lung, Pseudomonas aeruginosa is predominant, infecting over 50% of adults with CF, and becoming antibiotic-resistant over time. Current therapies for CF, while providing tremendous benefits, fail to eliminate persistent bacterial infections, chronic inflammation, and irreversible lung damage, necessitating novel therapeutic strategies. Our group engineered mesenchymal stromal cell derived extracellular vesicles (MSC EVs) to carry the microRNA let-7b-5p as a dual anti-infective and anti-inflammatory treatment. MSC EVs are low-immunogenicity platforms with innate antimicrobial and immunomodulatory properties, while let-7b-5p reduces inflammation. This study demonstrates that MSC EVs effectively blocked the formation of antibiotic-resistant P. aeruginosa biofilms on primary Human Bronchial Epithelial Cells (pHBECs), and let-7b-5p loading into MSC EVs conferred additional anti-inflammatory effects by reducing P. aeruginosa-induced IL-8 secretion by pHBECs. This approach holds promise for improving outcomes for people with CF, and future work will focus on optimizing delivery strategies and expanding the clinical applicability of MSC EVs to target other CF-associated pathogens.
期刊介绍:
The American Journal of Physiology-Lung Cellular and Molecular Physiology publishes original research covering the broad scope of molecular, cellular, and integrative aspects of normal and abnormal function of cells and components of the respiratory system. Areas of interest include conducting airways, pulmonary circulation, lung endothelial and epithelial cells, the pleura, neuroendocrine and immunologic cells in the lung, neural cells involved in control of breathing, and cells of the diaphragm and thoracic muscles. The processes to be covered in the Journal include gas-exchange, metabolic control at the cellular level, intracellular signaling, gene expression, genomics, macromolecules and their turnover, cell-cell and cell-matrix interactions, cell motility, secretory mechanisms, membrane function, surfactant, matrix components, mucus and lining materials, lung defenses, macrophage function, transport of salt, water and protein, development and differentiation of the respiratory system, and response to the environment.