Late Breaking Abstract - Evaluating the clinical potential of inhalation of umbilical cord mesenchymal stem cell (UC-MSC) exosomes in pulmonary fibrosis (PF) treatment.

• Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with limited treatment. Exosomes from UC-MSCs possess anti-fibrotic and regenerative properties. However, the therapeutic efficacy in treating PF remains underexplored. We explored the therapeutic potential of nebulized UC-MSC exosomes (Zen Zen biotech, Taiwan). C57BL/6 male mice intratracheally administered bleomycin (4U/kg) to induce PF. PF mice were treated with aerosolized 10¹⁰ particles/kg exosomes or placebo for 5 consecutive days. Lung function was measured through Flexivent (Scireq, Canada), and tissue morphology was identified using Masson Trichrome and hematoxylin and eosin (H&E) staining. Exosome-treated mice showed significantly improved lung function: 20% increased total lung capacity, 38% decreased resistance, and 40% improved compliance. The 105% decrease hydroxyproline analysis and a decline in lung-BW ratio indicated a reducing collagen accumulation. Histology revealed recovered alveolar structure. Exosome-treated mice lost only 2% body weight compared to 24% in controls. Aerosol inhalation provides a non-invasive exosome delivery to the lungs, increasing target site concentration and potentially achieving greater therapeutic effects. Our findings demonstrate the potential of inhaled exosomes for PF treatment, with future work focusing on mechanisms and optimization. <fig><object-id>erj;64/suppl_68/PA5169/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>