Human Placental Extract Enhances Neonatal Epithelial Reparative Capacity in Porcine Models
The devastation caused by necrotizing enterocolitis (NEC) has only continued to claim the lives of infants despite advances in neonatal medicine. To address the acute, and often severe, intestinal epithelial damage caused by NEC, therapeutics are needed that directly target epithelial recovery and cellular regeneration processes. Amniotic fluid and its derivatives have shown therapeutic benefit for NEC though these elements remain difficult to obtain. We therefore investigated the capacity of a decellularized human placental extract (HPE) comparable to amniotic fluid for its ability to prevent against and enhance recovery from NEC using in vitro and in vivo models. Healing responses of hypoxia or scratch-wound injured primary neonatal porcine ileal epithelial cells following HPE application were analyzed. In vivo, NEC was induced in neonatal piglets through a combination of preterm delivery and formula feeding.  Treated piglets received enteral HPE while control were nil per os prior to formula initiation. In vitro, HPE treatment accelerated scratch closure and increased proliferating cell number, without enhanced tight junction recovery following hypoxia. In vivo, HPE treatment increased weight gain, decreased macroscopic and histological damage, and increased ileal crypt epithelial cell proliferation. Transcriptomic analysis of monolayer cultures treated with HPE was undertaken after observation of similar effects in both in vitro and in vivo platforms. Increases in shared gene pathways associated with epithelial wound healing, proliferation, and migration were identified including members of the Wnt family.  In sum, these findings suggest that HPE can enhance the reparative capacity of neonatal epithelium in the context of NEC. Overall design: 2-3 replicates each of neonatal porcine ileal monolayers from 6 independent animals with and without Human Placental Extract (HPE) treatment