title: Human mesenchymal stem cells attenuate experimental bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia.
abstract: BACKGROUND
  Systemic maternal inflammation and neonatal hyperoxia arrest alveolarization in neonates. The aims were to test whether human mesenchymal stem cells (MSCs) reduce lung inflammation and improve lung development in perinatal inflammation- and hyperoxia-induced experimental bronchopulmonary dysplasia.
  
  
  METHODS
  Pregnant Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS, 0.5 mg/kg/day) on Gestational Days 20 and 21. Human MSCs (3×10(5) and 1×10(6) cells) in 0.03 ml normal saline (NS) were administered intratracheally on Postnatal Day 5. Pups were reared in room air (RA) or an oxygen-enriched atmosphere (O2) from Postnatal Days 1 to 14, and six study groups were obtained: LPS+RA+NS, LPS+RA+MSC (3×10(5) cells), LPS+RA+MSC (1×10(6) cells), LPS+O2+NS, LPS+O2+MSC (3×10(5) cells), and LPS+O2+MSC (1×10(6) cells). The lungs were excised for cytokine, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) expression, and histological analyses on Postnatal Day 14.
  
  
  RESULTS
  Body weight was significantly lower in rats reared in hyperoxia than in those reared in RA. The LPS+O2+NS group exhibited a significantly higher mean linear intercept (MLI) and collagen density and a significantly lower vascular density than the LPS+RA+NS group did. Administering MSC to hyperoxia-exposed rats improved MLI and vascular density and reduced tumor necrosis factor-α and interleukin-6 levels and collagen density to normoxic levels. This improvement in lung development and fibrosis was accompanied by an increase and decrease in lung VEGF and CTGF expression, respectively.
  
  
  CONCLUSIONS
  Human MSCs attenuated perinatal inflammation- and hyperoxia-induced defective alveolarization and angiogenesis and reduced lung fibrosis, likely through increased VEGF and decreased CTGF expression.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Hsiu-Chu
authors.initials: HC
authors.lastname: Chou
authors.affiliation: Meridigen Biotech Co., Ltd. Taipei, Taiwan.
authors.forename: Yuan-Tsung
authors.initials: YT
authors.lastname: Li
authors.affiliation: Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical UniversityTaipei, Taiwan; Department of Pediatrics, Taipei Medical University HospitalTaipei, Taiwan.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chen
keywords: Mesenchymal stem cells; connective tissue growth factor; hyperoxia; lipopolysaccharide; vascular endothelial growth factor