TY - JOUR
T1 - The effect of human amnion epithelial cells on lung development and inflammation in preterm lambs exposed to antenatal inflammation
AU - Papagianis, Paris Clarice
AU - Ahmadi-Noorbakhsh, Siavash
AU - Lim, Rebecca
AU - Wallace, Euan
AU - Polglase, Graeme
AU - Pillow, J. Jane
AU - Moss, Timothy J.
N1 - Funding Information:
This research was supported by an NHMRC Project Grant (1077769), NHMRC Centre for Research Excellence (1057514), two NHMRC Senior Research Fellowships (JJP; 1077691: TJM 1043294), the Victorian Government's Operational Infrastructure Support Program, and the West Australian Government's Medical and Health Research Infrastructure Fund. Unrestricted equipment and consumable support was provided by Chiesi Farmaceutici S.p.A. (poractant alfa); Fisher & Paykel Healthcare (ventilator circuits); and ICU Medical (arterial monitoring lines). None of the commercial industry funders had any input into study design, data collection and analysis, decision to publish or preparation of the manuscript. Chiesi Farmaceutici S.p.A. reviewed the final manuscript for technical accuracy pertaining to description and use of their surfactant, in accordance with a Material Transfer Agreement associated with the provision of surfactant for study animals. The University of Western Australia (via JJP) has consultancy agreements with Chiesi Farmaceutici S.p.A. unrelated to the subject of this study. Fisher & Paykel Healthcare have material transfer agreements with Hudson Research Institute that are also unrelated to this work. There are no other relevant interests relating to employment, consultancy, patents, or products in development or marketed products to declare. These material transfer agreements do not alter our adherence to PLOS ONE policies on sharing data and materials. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2021 Papagianis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Background Lung inflammation and impaired alveolarization are hallmarks of bronchopulmonary dysplasia (BPD). We hypothesize that human amnion epithelial cells (hAECs) are anti-inflammatory and reduce lung injury in preterm lambs born after antenatal exposure to inflammation. Methods Pregnant ewes received either intra-amniotic lipopolysaccharide (LPS, from E.coli 055:B5; 4mg) or saline (Sal) on day 126 of gestation. Lambs were delivered by cesarean section at 128 d gestation (term ~150 d). Lambs received intravenous hAECs (LPS/hAECs: n = 7; 30x106cells) or equivalent volumes of saline (LPS/Sal, n = 10; or Sal/Sal, n = 9) immediately after birth. Respiratory support was gradually de-escalated, aimed at early weaning from mechanical ventilation towards unassisted respiration. Lung tissue was collected 1 week after birth. Lung morphology was assessed and mRNA levels for inflammatory mediators were measured. Results Respiratory support required by LPS/hAEC lambs was not different to Sal/Sal or LPS/Sal lambs. Lung tissue:airspace ratio was lower in the LPS/Sal compared to Sal/Sal lambs (P<0.05), but not LPS/hAEC lambs. LPS/hAEC lambs tended to have increased septation in their lungs versus LPS/Sal (P = 0.08). Expression of inflammatory cytokines was highest in LPS/hAECs lambs. Conclusions Postnatal administration of a single dose of hAECs stimulates a pulmonary immune response without changing ventilator requirements in preterm lambs born after intrauterine inflammation.
AB - Background Lung inflammation and impaired alveolarization are hallmarks of bronchopulmonary dysplasia (BPD). We hypothesize that human amnion epithelial cells (hAECs) are anti-inflammatory and reduce lung injury in preterm lambs born after antenatal exposure to inflammation. Methods Pregnant ewes received either intra-amniotic lipopolysaccharide (LPS, from E.coli 055:B5; 4mg) or saline (Sal) on day 126 of gestation. Lambs were delivered by cesarean section at 128 d gestation (term ~150 d). Lambs received intravenous hAECs (LPS/hAECs: n = 7; 30x106cells) or equivalent volumes of saline (LPS/Sal, n = 10; or Sal/Sal, n = 9) immediately after birth. Respiratory support was gradually de-escalated, aimed at early weaning from mechanical ventilation towards unassisted respiration. Lung tissue was collected 1 week after birth. Lung morphology was assessed and mRNA levels for inflammatory mediators were measured. Results Respiratory support required by LPS/hAEC lambs was not different to Sal/Sal or LPS/Sal lambs. Lung tissue:airspace ratio was lower in the LPS/Sal compared to Sal/Sal lambs (P<0.05), but not LPS/hAEC lambs. LPS/hAEC lambs tended to have increased septation in their lungs versus LPS/Sal (P = 0.08). Expression of inflammatory cytokines was highest in LPS/hAECs lambs. Conclusions Postnatal administration of a single dose of hAECs stimulates a pulmonary immune response without changing ventilator requirements in preterm lambs born after intrauterine inflammation.
UR - http://www.scopus.com/inward/record.url?scp=85108696474&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0253456
DO - 10.1371/journal.pone.0253456
M3 - Article
C2 - 34170941
AN - SCOPUS:85108696474
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0253456
ER -