Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model

Julie Di Bernardo, Michael M. Maiden, Marc B. Hershenson, Shaun M. Kunisaki

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose 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.

Original languageEnglish (US)
Pages (from-to)859-865
Number of pages7
JournalJournal of pediatric surgery
Volume49
Issue number6
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • Amniotic fluid
  • Congenital diaphragmatic hernia
  • Lung development
  • Mesenchymal stem cell
  • Mesenchymal stromal cell
  • Nitrofen
  • Pulmonary hypoplasia

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health

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