Project description:Bronchopulmonary dysplasia remains one of the most common complication of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to access the lung and to maintain relevant stem cell populations in culture. Single cell RNA-sequencing confirmed the presence of epithelial cells in tracheal aspirates obtained from intubated neonates. Using combined SMAD signaling inhibition and mTOR inhibition neonatal tracheal-aspirate derived (nTAD) basal stem cells can be expanded long-term and retain the ability to differentiate into pseudo-stratified airway epithelium. Conclusions: Our data demonstrate that neonatal tracheal aspirate-derived epithelial cells can provide a novel ex vivo human cellular model to study neonatal lung development and disease.
Project description:Bronchopulmonary dysplasia remains one of the most common complication of prematurity, despite significant improvements in perinatal care. Functional modeling of human lung development and disease, like BPD, is limited by our ability to access the lung and to maintain relevant stem cell populations in culture. Single cell RNA-sequencing confirmed the presence of epithelial cells in tracheal aspirates obtained from intubated neonates. Using combined SMAD signaling inhibition and mTOR inhibition neonatal tracheal-aspirate derived (nTAD) basal stem cells can be expanded long-term and retain the ability to differentiate into pseudo-stratified airway epithelium. Conclusions: Our data demonstrate that neonatal tracheal aspirate-derived epithelial cells can provide a novel ex vivo human cellular model to study neonatal lung development and disease.
Project description:We performed global proteomics of premature infant tracheal aspirate (TA) and plasma to determine the composition and source of lung fluid proteins and to identify potential biomarkers of respiratory outcome
Project description:We conducted a prospective cohort study with independent Discovery and Validation cohorts, to formulate predictive biomarkers for Bronchopulmonary Dysplasia in extremely preterm infants. Tracheal aspirate samples were collected at birth from extremely preterm infants. Exosomes were extracted from tracheal aspirates and total RNA was extracted from these exosomes from individual samples. miRNA profiling for all ~ 800 miRNAs was conducted on each sample by nanostring platform. This study found that a distinct airway exosomal miRNA sigrature at birth (decreased miR 876-3p) predicts future development of severe Bronchopulmonary Dysplasia in extremely preterm infants.
Project description:Tracheal aspirate (TAs) samples were collected from intubated preterm infants with hemodynamically significant intracardiac shunt (ICS), and a diagnosis of ICS-BPD/ICS-BPD-PH. 36 TA samples were analyzed. Small RNAs were extracted and the expression miRNAs was detected with PCR arrays.
Project description:Ventilator associated pneumonia (VAP) is the 2nd most common hospital acquired infection associated with high morbidity, mortality and increased hospitalization. Current practice of diagnosis is based on clinical symptoms and bronchoalvolar lavage (BAL) culture. The procedures of BAL collections are invasive whereas, endotracheal aspirate (ETA), a matrix of upper airway collection is minimally invasive and underexplored in VAP diagnosis. The study describes first in detail characterization of proteome of longitudinal ETA collections from 16 intubated patients including 11 VAP patients and explores potential utility of ETA in VAP diagnosis.
Project description:To understand the molecular mechanisms of human lung macrophage development, function, and role in BPD pathogenesis, we conducted a clinical study using isolated tracheal aspirate macrophages from intubated preterm infants born before 30 wk gestation. One hundred twenty-eight patients intubated for respiratory distress syndrome and surfactant administration were consented for the study.
