title: Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.
abstract: OBJECTIVE
  Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model.
  
  
  METHODS
  Pregnant Sprague-Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression.
  
  
  RESULTS
  Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs.
  
  
  CONCLUSIONS
  AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia.
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Di Bernardo
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Maiden
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
authors.affiliation: Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA. Electronic address: shaunkun@umich.edu.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Kunisaki
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000196:embryology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D038081:Organogenesis / Q000187:drug effects*; D010647:Phenyl Ethers / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010647:Phenyl Ethers; C007350:nitrofen
keywords: Amniotic fluid; Congenital diaphragmatic hernia; Lung development; Mesenchymal stem cell; Mesenchymal stromal cell; Nitrofen; Pulmonary hypoplasia