139 - Mesenchymal Stem Cell-derived Exosomes in Tracheal Aspirate Fluid of Preterm Infants Prevent Bronchopulmonary Dysplasia via Suppression of Lung Inflammation

Poster Number: 139
Publication Number: 139.436

Smrithy Jacob, University of California, Irvine, School of Medicine, Orange, CA, United States; Cherry Uy, University of California, Irvine, School of Medicine, Orange, CA, United States; Fayez Bany-Mohammed, University of California, Irvine, School of Medicine, Orange, CA, United States; Muhammad Aslam, University of California, Irvine, School of Medicine, Orange, CA, United States

Background: Bronchopulmonary dysplasia (BPD) in preterm infants leads to arrested alveolar development with significant morbidity and mortality. Our published work has shown prevention and treatment of murine experimental BPD with mesenchymal stem cell (MSC)-derived exosomes. Exosomes are extracellular vesicles involved in cell-to-cell communication, cell signaling, and altering cell or tissue responses to injury, infection, and disease. MSC-derived exosomes are packed with cytokines, growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Our current study evaluates the role of MSC-derived exosomes in the tracheal aspirate fluid (TAF) of preterm infants in prevention of BPD.

Objective: We hypothesized that lack of MSC-derived exosomes in TAF of preterm infants at birth leads to development of BPD via uncontrolled inflammation with TGF- β1 activity. Our objectives were to detect the presence of MSC-derived exosomes and active TGF-β1 in the TAF of preterm infants in the first week of life and correlate them with later development and severity of BPD.

Design/Methods: Infants less than 32 weeks’ gestational age and/or less than 1500 grams at birth who were intubated within 24 hours of life were enrolled into the study. The first TAF sample was obtained at intubation before any exogenous surfactant administration. The second sample was obtained at extubation or on the 4th day of life if still intubated. The TAF samples were processed per our published protocols to detect exosomes. The levels of TGF-β1 were analyzed using immunoassay. Infants were followed prospectively for outcome data including the development and severity of BPD at 36 weeks’ corrected gestational age.

Results: To date, we have enrolled 52 preterm infants into the study and TAF samples have been collected along with baseline maternal and infant characteristics. 22 of these 52 infants had their TAF samples analyzed. Subjects were similar in their baseline maternal and neonatal characteristics (Figure 1). 9 of 22 infants developed BPD. Infants with BPD had lower exosomes count in TAF in both samples compared with infants who did not develop BPD (11+/- 2 vs. 23+/-2 in sample 1, and 8+/-1 vs. 26+/-2 in sample 2). Infants with BPD who had lower exosome count also failed to suppress M1 macrophage surge with a higher TGF-β1 levels when compared with infants without BPD with higher exosomes count (Figure 2). All results were statistically significant.

Conclusion(s): MSC-derived exosomes prevent BPD at birth by suppression of lung inflammation (M1 macrophage surge and active TGF-β1). Further data and exosome content analysis is currently in progress.