325 - Targeted Inhalation of Human Preterm Mesenchymal Stem Cell Exosomes for Experimental Bronchopulmonary Dysplasia Therapy

Publication Number: 1309.325

Caitlin E. Jackson, University of California, Irvine, School of Medicine, Orange, CA, United States; Fayez Bany-Mohammed, University of California, Irvine, Irvine, CA, United States; Cherry Uy, University of California, Irvine, School of Medicine, Orange, CA, United States; Muhammad Aslam, UC Irvine, Orange, CA, United States

Background: Bronchopulmonary dysplasia (BPD) is a chronic, debilitating lung disease in preterm infants characterized by impaired alveolarization and pulmonary hypertension. Our previous work demonstrated that intravenous administration of mesenchymal stem cells (MSCs) and their exosomes (MSC-exo) decrease murine BPD. Direct delivery to the lungs may improve local concentration, reduce systemic exposure, and enhance therapeutic efficiency. This study evaluated the effectiveness of inhaled preterm MSC-exo in reversing established murine BPD.

Objective: We hypothesized that inhalation of preterm MSC-exo would be therapeutically effective in established murine BPD. We assessed lung and heart injury in hyperoxia-exposed mice treated with MSC-exo inhalation.

Design/Methods: MSCs and MSC-exo were generated from preterm umbilical cords (24-28 weeks' gestation). FVB mice were exposed to hyperoxia (90% O₂) within 24 hours of birth; controls remained in normoxia (21% O₂). At day 14, all animals returned to normoxia. Weekly inhalation therapy with preterm MSC-exo (0.1 µg/g body weight) began at 4 weeks of age. Controls received human skin epithelial cell exosomes (SEC-exo). Pulmonary function testing (PFT) and echocardiography were performed biweekly until 3 months of age.

Results: Baseline PFT and echo at day 28 confirmed hyperoxia-induced BPD, with reduced lung function and pulmonary hypertension. Weekly MSC-exo inhalation led to progressive recovery, achieving approximately 50% improvement by 3 months. Treated mice showed increased lung inspiratory capacity and compliance compared with SEC-exo controls (Fig. 1). Inhalation therapy also partially prevented pulmonary hypertension, with reduced right ventricular hypertrophy and improved pulmonary artery acceleration time (Fig. 2). All findings were statistically significant.

Conclusion(s): Inhaled MSC-exo therapy is feasible and partially reverses established murine BPD, improving both lung function and pulmonary vascular outcomes. These results support the potential of inhaled MSC-exo as a targeted therapy for BPD. Ongoing studies will evaluate longer treatment duration and confirm these findings.

Figure 1
Pulmonary Function Test in Treated Animals

Figure 2
Echocardiogram Findings in Treated Animals