title: Tracheal Aspirate Levels of the Matricellular Protein SPARC Predict Development of Bronchopulmonary Dysplasia.
abstract: BACKGROUND
  Isolation of tracheal aspirate mesenchymal stromal cells (MSCs) from premature infants has been associated with increased risk of bronchopulmonary dysplasia (BPD). MSCs show high levels of mRNAs encoding matricellular proteins, non-structural extracellular proteins that regulate cell-matrix interactions and participate in tissue remodeling. We hypothesized that lung matricellular protein expression predicts BPD development.
  
  
  METHODS
  We collected tracheal aspirates and MSCs from mechanically-ventilated premature infants during the first week of life. Tracheal aspirate and MSC-conditioned media were analyzed for seven matricellular proteins including SPARC (for Secreted Protein, Acidic, Rich in Cysteine, also called osteonectin) and normalized to secretory component of IgA. A multiple logistic regression model was used to determine whether tracheal aspirate matricellular protein levels were independent predictors of BPD or death, controlling for gestational age (GA) and birth weight (BW).
  
  
  RESULTS
  We collected aspirates from 89 babies (38 developed BPD, 16 died before 36 wks post-conceptual age). MSC-conditioned media showed no differences in matricellular protein abundance between cells from patients developing BPD and cells from patients who did not. However, SPARC levels were higher in tracheal aspirates from babies with an outcome of BPD or death (p<0.01). Further, our logistic model showed that tracheal aspirate SPARC (p<0.02) was an independent predictor of BPD/death. SPARC deposition was increased in the lungs of patients with BPD.
  
  
  CONCLUSIONS
  In mechanically-ventilated premature infants, tracheal aspirate SPARC levels predicted development of BPD or death. Further study is needed to determine the value of SPARC as a biomarker or therapeutic target in BPD.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Antonia P
authors.initials: AP
authors.lastname: Popova
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Tracy X
authors.initials: TX
authors.lastname: Cui
authors.affiliation: Center for Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.|Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Niko
authors.initials: N
authors.lastname: Kaciroti
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Goldsmith
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Marisa J
authors.initials: MJ
authors.lastname: Linn
authors.affiliation: Department of Pediatrics, University of Rochester, Rochester, New York, United States of America.
authors.forename: Gloria S
authors.initials: GS
authors.lastname: Pryhuber
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, United States of America.|Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000378:metabolism* / Q000473:pathology*; D002469:Cell Separation; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D015676:Osteonectin / Q000378:metabolism*; D013396:Suction; D014132:Trachea / Q000378:metabolism*
chemical_list: D015676:Osteonectin