The effect of human amnion epithelial cells on lung development and inflammation in preterm lambs exposed to antenatal inflammation

Abstract

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; 30x106 cells) 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.

Multipotent adult progenitor cells prevent functional impairment and improve development in inflammation driven detriment of preterm ovine lungs

“…Namely, the improvement of lung function was preceded by enhanced acinar development after MAPC therapy, designated by increased RAC and TTF-1+ cells in LPS-exposed and MAPC-treated animals, indicating that an improved lung architecture in concert with the reduction of edema is responsible for the improvement of lung function. This concept is supported by earlier findings showing that MSC treatment accelerated pulmonary growth and regeneration in injured preterm lungs of mice and sheep [ 17 , 45 ]. For instance, a preterm lamb model of antenatal inflammation reported improved alveolar development by endorsing alveolar growth and differentiation after MSC treatment [ 17 ].…”

“…At 132 dGA, fetuses were surgically delivered, which was followed by oral intubation with an endotracheal tube, umbilical cord clamping and the lambs were weighted. Lambs were transitioned to an infant radiator bed (IW930 Series, Cosy-Cots™ Infant Warmer, Fisher&Paykel, Auckland, NZ), where they were dried and placed in a sling [ 17 ]. The lamb was immediately connected to an infant ventilation device (Fabian HFO®; Acutronic, Hirzel, CH) [ 18 ].…”

Hydrogen gas ameliorates the LPS-induced BPD via inhibiting the activation of TNF-α/NF-κB inflammatory signaling pathway in placenta

“…Intra-amniotic administration of LPS at E16.5 to induce in ammatory cascades-CAM is similar to the major clinical characteristics observed in patients with BPD. CAM can produce excessive in ammatory factors into the fetus, which affect the maturation of fetal lung, cause fetal lung structural remodeling, affect the contractile function of pulmonary vessels, and thus lead to the occurrence of BPD [21,22]. Our results indicated that LPS group exhibited a disorder of intrauterine development: the intrauterine fatal death (IUFD) rates represented a high level in the LPS group.…”

Hydrogen gas inhalation ameliorates LPS-induced BPD by inhibiting inflammation via regulating the TLR4–NFκB–IL6/NLRP3 signaling pathway in the placenta

“…However, the model still has drawbacks such as complex experimental operations, significant trauma, and susceptibility to infection. CAM can produce excessive inflammatory factors in the fetus, which affect the maturation of the fetal lung, cause fetal lung structural remodeling, and affect the contractile function of pulmonary vessels, thus leading to the occurrence of BPD [ 19 , 20 ]. Our results indicated that the LPS group exhibited a disorder of intrauterine development: intrauterine fetal death (IUFD) rates were high in the LPS group.…”