577 - Regulatory MicroRNAs in Mesenchymal Stem Cell Exosomes from Tracheal Aspirate Fluid of Preterm Infants Prevent Bronchopulmonary Dysplasia

Poster Number: 577
Publication Number: 577.1284

Background: Bronchopulmonary dysplasia (BPD) is a debilitating disease of preterm infants with long term morbidity and high mortality. Our published work has shown prevention and treatment of murine experimental BPD with mesenchymal stem cells (MSC). Exosomes are extracellular vesicles involved in cell-to-cell communication, cell signaling, and altering cell or tissue responses to injury, infection, and disease. MSC-exosomes (MSC-exo) are packed with cytokines and growth factors, signaling lipids, mRNAs, and regulatory microRNAs (miRNAs). This study evaluated the role of MSC-exo in the tracheal aspirate fluid (TAF) of preterm infants in the prevention of BPD.

Objective: We hypothesized that the lack of MSC-exo regulatory miRNAs in TAF of preterm infants at birth leads to the development of BPD via uncontrolled inflammation with TGF-β1 activity. Our objectives were to detect the presence of MSC-exo miRNAs 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 born at less than 32 weeks’ gestational age and/or less than 1500 grams and were intubated within 24 hours of life were enrolled. The first TAF sample was obtained at intubation before exogenous surfactant administration. The second sample was obtained at extubation or on the 4th day of life. TAF MSC-exo were isolated and expressed markers of CD9, CD 63, and flotillin -1. TaqMan MicroRNA Array kit was used to identify miRNAs. The levels of TGF- β1 were analyzed using immunoassay. Infants were followed prospectively for outcome data including the development of BPD.

Results: We have enrolled 52 preterm infants and collected TAF samples and baseline maternal and infant characteristics. 22 of these 52 infants (9 BPD and 13 non-BPD) had their TAF samples analyzed, and data completed. The subjects were similar in their baseline maternal and neonatal characteristics (Figure 1). Infants with BPD had lower exosome counts in TAF in both samples compared with infants who did not develop BPD. Infants with BPD had higher TGF- β1 levels when compared with infants without BPD (Figure 2). MiRNAs differed in MSC-exo between BPD and non-BPD groups (Figure 3). BPD MSC-exo miRNAs are involved in inflammation, cell injury, and apoptosis. Non-BPD MSC-exo miRNAs have been shown to prevent injury and inflammation via suppression of macrophages and TGF-β1 surge.

Conclusion(s): MSC-derived exosomes prevent BPD by the suppression of lung inflammation via miRNAs transfer leading to inhibition of cell injury and inflammation. Further data and exosome content analysis is in progress.