title: Human amnion epithelial cells as a treatment for inflammation-induced fetal lung injury in sheep.
abstract: OBJECTIVE
  The purpose of this study was to determine whether human amnion epithelial cells (hAECs) can modulate the pulmonary developmental consequences of intrauterine inflammation in fetal sheep that are exposed to intraamniotic lipopolysaccharide (LPS) injection.
  
  
  METHODS
  At 117 days' gestation, fetal sheep (n=16) received intraamniotic LPS (20 mg). hAECs were delivered at 0, 6, and 12 hours into the fetal jugular vein (n=4), trachea (n=4), or both (n=4). Controls (n=6) received equivalent administration of saline solution. Lungs were collected at 124 days.
  
  
  RESULTS
  Intraamniotic LPS caused pulmonary inflammation and altered lung structure and function. hAECs attenuated changes in lung function and structure that had been induced by LPS: lung volume, 40 cm H2O (P<.05, intravenous+intratracheal hAECs vs LPS), tissue-to-airspace ratio (P<.05, intravenous+intratracheal hAECs vs LPS), and septal crest density (P<.001, all hAEC groups vs LPS). Leukocyte infiltration of the lungs was not reduced by hAECs; however, inflammatory cytokines were reduced (tumor necrosis factor-α, P<.01, vs LPS; interleukin-1b, P<.01, vs LPS; interleukin-6, P<.01 vs LPS). Surfactant protein A and C messenger RNA was increased by LPS, although this was not statistically significant (P>.05 vs control); there were significant increases in all hAEC-treated animals (surfactant protein-A, P<.05 vs LPS; surfactant protein-C, P<.01 vs LPS).
  
  
  CONCLUSIONS
  Human amnion epithelial cells attenuate the fetal pulmonary inflammatory response to experimental intrauterine inflammation and reduce, but (as administered in our study) do not prevent, consequent alterations in lung development.
authors.affiliation: The Ritchie Centre, Monash Institute of Medical Research, Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Vosdoganes
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Hodges
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.forename: Alana J
authors.initials: AJ
authors.lastname: Westover
authors.forename: Rutu Y
authors.initials: RY
authors.lastname: Acharya
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
mesh_terms: D000650:Amnion; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000637:transplantation*; D005260:Female; D005315:Fetal Diseases / Q000628:therapy; D006801:Humans; D007267:Injections; D008070:Lipopolysaccharides / Q000494:pharmacology; D055370:Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D012756:Sheep; D034561:Sheep, Domestic; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D008070:Lipopolysaccharides