465 - Mesenchymal Stem Cell Biomarkers Prevent Neonatal Chronic Lung Disease via Suppression of Lung Inflammation

Poster Number: 465
Publication Number: 465.432

Smrithy Jacob, University of California, Irvine, School of Medicine, Huntington Beach, CA, United States; Fayez M. Bany-Mohammed, UC Irvine Medical Center, Orange, CA, United States; Cherry Uy, 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: Neonatal chronic lung disease also known as bronchopulmonary dysplasia (BPD) is a disease of preterm infants leading to arrested alveolar development with long term morbidity and high mortality. Current therapies lack effectiveness and cause undesirable side effects. Our published work has shown prevention and treatment of murine experimental BPD with human umbilical cord mesenchymal stem cell (MSC) secreted biomarkers Osteopontin (Opn) and Colony stimulating factor 1 (Csf1) via suppression of lung inflammation (active TGF-β1 surge). Current study evaluated the stem cell secreted factors in the tracheal aspirate fluid (TAF) of preterm infants in prevention of BPD. 

Objective: We hypothesized that the lack of MSC biomarkers at birth leads to development of BPD via uncontrolled inflammation with uncontrolled TGF-β1 activity. Our objectives were to determine the levels of Opn, Csf1, 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: The study was approved by Institutional IRB. Infants < 32 weeks’ gestation and/or < 1500 gms birth weight 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. Levels of Opn, Csf1, TGF-β1, and secretory IgA were analyzed using immunoassay. Secretory IgA was used as control to correct for TAF volume. Infants were followed prospectively for outcome data including the development of BPD (oxygen requirement at 36 weeks’ corrected gestational age).

Results: From January 2015 to June 2018, a total of 52 preterm infants were enrolled into the study and TAF samples obtained. Baseline maternal and neonatal data as well as ventilation details are presented in Figure 1. BPD infants had lower birth weight compared to non-BPD infants and they also had longer ventilation days. Standard curves were used from our pilot study to analyze data. 20 of 52 infants developed BPD. Immunoassay results are shown in Figure 2. Pre- and post-ventilation levels of Opn and Csf1 were lower at birth for BPD infants when compared with infants who did not develop BPD. BPD infants failed to suppress M1 macrophage surge with a higher TGF-β1 levels when compared with infants who did not develop BPD. All results were statistically significant as shown in Figures 1 and 2. Conclusion(s): MSC biomarkers, Opn and Csf1, prevent BPD at birth by suppression of lung inflammation (M1 macrophage surge and active TGF-β1). 
Figure 1: Maternal and Neonatal CharacteristicsPAS Figure 1.jpegDemographic Features of Patients According to the Development of Bronchopulmonary Dysplasia
Figure 2: Immunoassay for BiomarkersPAS Figure 2.jpegImmunoassay Results for Biomarkers in BPD and non-BPD groups