Adipocyte Mesenchymal Stem Cells Derived Exosomes Improve Bleomycin‐Induced Lung Fibrosis in Rat

ABSTRACT Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease with limited treatment options. Although extracellular vesicles (EVs), such as exosomes, have shown therapeutic potential, their effectiveness and the best method of delivery are still under investigation. This study explored the therapeutic impact of exosomes derived from adipose‐derived mesenchymal stem cells (ADMSCs‐Exo) in a rat model of bleomycin‐induced pulmonary fibrosis. Methods Thirty Wistar rats were randomly divided into six groups: (1) Healthy control (Co), (2) Fibrosis control (Co/F), (3 and 4) Exosome inhalation groups treated with 250 or 500 μg/kg doses, and (5 and 6) Exosome injection groups receiving the same doses. Treatment effects were evaluated through lung tissue histopathology and analysis of key inflammatory biomarkers. Results The inhalation of ADMSCs‐Exo at both doses significantly reduced levels of C‐reactive protein (CRP), fibrinogen, pro‐inflammatory cytokines, and histopathological signs of lung fibrosis compared to the fibrosis control group ( p < 0.05). Notably, the inhalation route showed better therapeutic outcomes than systemic injection. Conclusion The results suggest that inhalation delivery of ADMSCs‐derived exosomes may provide a more effective and targeted strategy for treating pulmonary fibrosis compared to systemic administration.