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Published on: July 28, 2022
Human Placental Extract Enhances Neonatal Intestinal Epithelial Reparative Capacity in Porcine Models
Caroline A McKinney-Aguirre1, Amy S Stewart1, John M Freund1
1Department of Clinical Sciences, North Carolina State University, Raleigh, North Carolina.
Insights
Necrotizing enterocolitis (NEC) is a devastating condition in infants. Human placental extract (HPE) shows promise in promoting intestinal epithelial healing and regeneration in NEC models.
Area of Science:
- Neonatal Medicine
- Gastroenterology
- Regenerative Medicine
Background:
- Necrotizing enterocolitis (NEC) poses a significant threat to infant survival.
- Current neonatal medicine lacks targeted therapies for intestinal epithelial damage in NEC.
- There is a critical need for therapeutics that promote epithelial repair and regeneration.
Purpose of the Study:
- To investigate the potential of decellularized human placental extract (HPE) in preventing and treating NEC-induced intestinal injury.
- To evaluate HPE's efficacy in promoting epithelial recovery and cellular regeneration in both in vitro and in vivo NEC models.
Main Methods:
- In vitro studies utilized primary neonatal porcine ileal epithelial cells subjected to hypoxia or scratch-wound injury with HPE treatment.
- In vivo studies involved inducing NEC in neonatal piglets and administering enteral HPE.
- Transcriptomic analysis was performed on HPE-treated monolayer cultures to identify key molecular pathways involved in healing.
Main Results:
- In vitro, HPE accelerated epithelial scratch closure and increased cell proliferation but did not improve tight junction recovery after hypoxia.
- In piglets, HPE administration led to increased weight gain, reduced NEC-related damage, and enhanced ileal crypt cell proliferation.
- Transcriptomic analysis revealed that HPE upregulates pathways crucial for epithelial wound healing, proliferation, and migration.
Conclusions:
- Decellularized human placental extract (HPE) demonstrates potential in enhancing the intestinal epithelium's reparative capacity.
- HPE may serve as a novel therapeutic agent for managing necrotizing enterocolitis (NEC) in infants.
- Further research into HPE's mechanisms and clinical application for NEC is warranted.
Background & Aims:
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.
Methods:
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.
Results:
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 animals had nothing by mouth 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.
Conclusions:
In sum, these findings suggest that HPE can enhance the reparative capacity of neonatal epithelium in the context of NEC.
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