Human Placental Extract Enhances Neonatal Intestinal Epithelial Reparative Capacity in Porcine Models

The devastation caused by necrotizing enterocolitis (NEC) has 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 that directly target epithelial recovery and cellular regeneration processes are needed. We investigated the capacity of a decellularized human placental extract (HPE) to prevent and enhance recovery from NEC-like injury using in vitro and in vivo models. Healing responses in primary neonatal porcine ileal epithelial cells were analyzed following hypoxia or scratch-wound injury and HPE application. In vitro, HPE treatment accelerated scratch closure and increased proliferating cell number though did not enhance tight junction recovery following hypoxia. 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 piglets, HPE treatment increased weight gain, decreased macroscopic and histological damage, and increased ileal crypt epithelial cell proliferation. After observation of similar effects using in vitro and in vivo platforms, transcriptomic analysis of monolayer cultures treated with HPE was undertaken. Increased expression of pathways associated with epithelial wound healing, proliferation, and migration were identified, with key shared genes between those pathways. In sum, these findings suggest that HPE can enhance the reparative capacity of neonatal epithelium in the context of NEC.