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. STUDY DESIGN: 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 H(2)O (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-alpha, 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). CONCLUSION: 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.
Vosdoganes, P., Hodges, R., Lim, R., Westover, A., Acharya, R., Wallace, E., & Moss, T. (2011). Human amnion epithelial cells as a treatment for inflammation-induced fetal lung injury in sheep. American Journal of Obstetrics and Gynecology, 205(2 (Art. No: 156)), e26 - e33. https://doi.org/10.1016/j.ajog.2011.03.054