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Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 h into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum were assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of critical progenitor/stem cell and Paneth cell populations in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared with NEC littermates. Further, the intestinal stem cell and crypt niche that include Paneth cells, SOX9 + cells, and LGR5 + stem cells were restored with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage. NEW & NOTEWORTHY These studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can be utilized to elucidate critical neonatal repair mechanisms to overcome NEC.
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This content will become publicly available on November 11, 2025
Necrotizing Enterocolitis Detection in Premature Infants Using Broadband Optical Spectroscopy
ABSTRACT Necrotizing enterocolitis (NEC) is a devastating disease affecting premature infants. Broadband optical spectroscopy (BOS) is a method of noninvasive optical data collection from intra‐abdominal organs in premature infants, offering potential for disease detection. Herein, a novel machine learning approach, iterative principal component analysis (iPCA), is developed to select optimal wavelengths from BOS data collected in vivo from neonatal intensive care unit (NICU) patients for NEC classification. Neural network models were trained for classification, with a reduced‐feature model distinguishing NEC with an accuracy of 88%, a sensitivity of 89%, and a specificity of 88%. While whole‐spectrum models performed the best for accuracy and specificity, a reduced feature model excelled in sensitivity, with minimal cost to other metrics. This research supports the hypothesis that the analysis of human tissue via BOS may permit noninvasive disease detection. Furthermore, a medical device optimized with these models may potentially screen for NEC with as few as seven wavelengths.
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- Award ID(s):
- 1830961
- PAR ID:
- 10558229
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Journal of Biophotonics
- ISSN:
- 1864-063X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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