Human Amnion Epithelial Cells Modulate Ventilation-Induced White Matter Pathology in Preterm Lambs

Area of Science:

• Neonatal neurology
• Regenerative medicine
• Biomarker research

Background:

• Preterm infants undergoing resuscitation may experience high tidal volume (VT) ventilation.
• This high VT ventilation can cause cerebral white matter (WM) pathology, similar to that seen in infants with cerebral palsy.
• Human amnion epithelial cells (hAECs) possess anti-inflammatory and regenerative properties.

Purpose of the Study:

• To investigate if hAECs can mitigate ventilation-induced WM pathology in neonatal late preterm lamb brains.
• To assess the impact of hAECs on inflammation, vascular leakage, and astrogliosis in the developing brain.

Main Methods:

• Late preterm lambs (0.85 gestation) were divided into ventilated (Vent) and ventilated + hAECs (Vent+hAECs) groups.
• The Vent group received injurious ventilation (VT 15 ml/kg), while the Vent+hAECs group received hAECs intravenously and intratracheally at birth.
• Quantitative real-time PCR (qPCR) and immunohistochemistry were used to analyze WM pathology, inflammation, and vascular markers.

Main Results:

• hAEC administration reduced IL-6 mRNA in subcortical WM and decreased microglial density in the parietal lobe's subcortical WM.
• A reduction in protein extravasation in parietal lobe WM vessels was observed in the Vent+hAECs group.
• Claudin-1 mRNA levels increased in periventricular WM, suggesting altered vascular integrity.

Conclusions:

• hAEC administration at birth modifies the brain's response to injurious ventilation in preterm neonates.
• The study highlights regional differences in hAEC effects on WM pathology.
• Further investigation is required to determine the overall impact of hAECs on the developing brain.