Background: Neonatal resuscitation of preterm infants can inadvertently cause lung and brain injury and inflammation, which is linked to adverse outcomes including bronchopulmonary dysplasia and cerebral palsy. We hypothesized that human amnion epithelial cells (hAECs), due to their anti-inflammatory and regenerative properties, would mitigate ventilator-induced brain injury and inflammation in preterm lambs.
Methods: Three groups of lambs (0.85 gestation) were used: (i) Ventilated lambs (Vent; n=8) were injuriously resuscitated (tidal volume targeting 15 mL/kg, no positive end-expiratory pressure) and then gently ventilated for 105 min; (ii) Ventilation+hAECs lambs (n=7) were similarly ventilated but received intravenous and intratracheal administration of 9x107 hAECs (total 18x107). (iii) Unventilated control lambs (UVC; n=9) were killed immediately. Brain inflammation… was assessed in periventricular and subcortical white matter of the frontal and parietal lobes using immunohistochemistry and qRT-PCR. One-way ANOVA was used to compare groups.
Results: The numbers of microglia in the periventricular white matter of the frontal and parietal lobes was not different between groups. The number of microglia in the subcortical white matter tended lower in the frontal lobe in the hAECs group compared to Vent (p=0.065). Occludin mRNA expression in the frontal lobe was higher in both the Vent and hAECs groups compared to UVC (p=0.024) with a similar trend seen in the parietal lobe (p=0.071). Qualitative assessment of vascular leakage indicated fewer leaky vessels in the hAECs group compared to UVC and Vent. HIF-1a and PECAM mRNA was higher in hAECs compared to UVC (p=0.052 and p=0.034, respectively).
Conclusions: hAECs have not maintained their anti-inflammatory properties but have the potential to increase the integrity of the blood brain barrier. hAECs have increased expression of hypoxic markers within the angiogenic pathway.