Background Necrotizing enterocolitis (NEC) is a devastating condition associated with long-term complications including NDI (neurodevelopmental impairment), chronic lung disease, and intestinal complications. Umbilical-cord-derived mesenchymal stem cells (USCs) have been shown to improve intestinal outcomes when given prophylactically in preclinical NEC models. We hypothesized that intervention with USCs following onset of experimental NEC would also improve outcomes. Methods NEC was induced in 5-day-old mouse pups through formula gavage, hypoxia, and hypothermia. Control pups were left with mother (BF ctrl, n = 21). Experimental animals were given an intraperitoneal (IP) injection of either USCs (NEC + USC, n = 16) or sterile PBS (NEC + PBS, n = 18) on PND(postnatal) 7. On PND 9, pups were euthanized, intestinal and lung tissues were H&E stained and homogenized for cytokine assessment, while brain microglia were analyzed via immunohistochemistry. Results When compared to the NEC + PBS group, the NEC + USC group showed improved clinical scores, intestinal and lung histology, and an improved cytokine profile. Brain microglia were more characteristic of a resting state, with increased branching and complexity that was similar to breast-fed controls. Conclusions These findings suggest that intraperitoneal USC administration after NEC onset improves clinical outcomes and reduces intestinal, pulmonary, and neuronal injury—highlighting its potential as a therapy after onset of experimental NEC. Impact <UnorderedList Mark="Bullet"> <ItemContent> Umbilical-cord-derived mesenchymal stem cells (USCs) can improve outcomes in NEC even after its onset. </ItemContent> <ItemContent> This study is the first murine model to show that USCs serve as an effective rescue therapy—demonstrating significant improvements in clinical scores, intestinal health, lung function, and brain microglia activity. </ItemContent> <ItemContent> The research suggests that IP USCs may reduce secondary organ damage and enhance long-term outcomes for affected infants, paving the way for future pre-clinical and clinical trials in the neonatal care of this devastating disease. </ItemContent> </UnorderedList>

Intraperitoneal rescue stem cell therapy in experimental NEC mitigates intestinal, pulmonary, and neuroinflammatory injury in mice

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2025年12月2日

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Krishna Manohar,
Fikir M. Mesfin,
Sharon Joseph,
Jasmine Lee,
Jianyun Liu,
William Chris Shelley,
John P. Brokaw,
Troy A. Markel

摘要

Background

Necrotizing enterocolitis (NEC) is a devastating condition associated with long-term complications including NDI (neurodevelopmental impairment), chronic lung disease, and intestinal complications. Umbilical-cord-derived mesenchymal stem cells (USCs) have been shown to improve intestinal outcomes when given prophylactically in preclinical NEC models. We hypothesized that intervention with USCs following onset of experimental NEC would also improve outcomes.

Methods

NEC was induced in 5-day-old mouse pups through formula gavage, hypoxia, and hypothermia. Control pups were left with mother (BF ctrl, n = 21). Experimental animals were given an intraperitoneal (IP) injection of either USCs (NEC + USC, n = 16) or sterile PBS (NEC + PBS, n = 18) on PND(postnatal) 7. On PND 9, pups were euthanized, intestinal and lung tissues were H&E stained and homogenized for cytokine assessment, while brain microglia were analyzed via immunohistochemistry.

Results

When compared to the NEC + PBS group, the NEC + USC group showed improved clinical scores, intestinal and lung histology, and an improved cytokine profile. Brain microglia were more characteristic of a resting state, with increased branching and complexity that was similar to breast-fed controls.

Conclusions

These findings suggest that intraperitoneal USC administration after NEC onset improves clinical outcomes and reduces intestinal, pulmonary, and neuronal injury—highlighting its potential as a therapy after onset of experimental NEC.

Impact

Umbilical-cord-derived mesenchymal stem cells (USCs) can improve outcomes in NEC even after its onset.

This study is the first murine model to show that USCs serve as an effective rescue therapy—demonstrating significant improvements in clinical scores, intestinal health, lung function, and brain microglia activity.

The research suggests that IP USCs may reduce secondary organ damage and enhance long-term outcomes for affected infants, paving the way for future pre-clinical and clinical trials in the neonatal care of this devastating disease.