title: Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury.
abstract: BACKGROUND
  Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis.
  
  
  METHODS
  Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 μg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay.
  
  
  RESULTS
  As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs.
  
  
  CONCLUSIONS
  Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis.
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Miranda
authors.affiliation: 1] Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida [2] Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Claudia O
authors.initials: CO
authors.lastname: Rodrigues
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Shalini
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Eneida
authors.initials: E
authors.lastname: Torres
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Jammie
authors.initials: J
authors.lastname: Klim
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hehre
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.affiliation: 1] Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida [2] Cardiovascular Division, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Cleide Y
authors.initials: CY
authors.lastname: Suguihara
authors.affiliation: 1] Department of Pediatrics, University of Miami Miller School of Medicine, Miami, Florida [2] Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, Florida [3] Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Young
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018496:Hyperoxia / Q000188:drug therapy* / Q000503:physiopathology; D055370:Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010919:Placebos; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010919:Placebos; D019089:Stem Cell Factor