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Peer-reviewed veterinary case report

Intestinal stem cell-derived extracellular vesicles ameliorate necrotizing enterocolitis injury.

Journal:
Molecular and cellular probes
Year:
2025
Authors:
Zhang, Le et al.
Affiliation:
Department of Neonatology · China
Species:
rodent

Abstract

The therapeutic potential of intestinal stem cell-derived extracellular vesicles (ISCs-EVs) in necrotizing enterocolitis (NEC) remains largely unexplored. This research aims to investigate the therapeutic effects of ISCs-EVs on NEC. Lgr5-positive ISCs were screened from the small intestine of mice by flow cytometry, and ISCs-EVs were isolated by density gradient centrifugation. Subsequently, ISCs-EVs were identified through transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Subsequently, we evaluated the efficacy of ISCs-EVs in a mouse model of NEC and found that they enhanced survival (more than 20&#xa0;%), reduced intestinal damage (restore the number of intestinal crypts and decrease the expression of MPO and cleaved-caspase 3 in intestinal tissues), promoted angiogenesis (the mRNA expression of VEGF was increased by approximately 35&#xa0;%), and mitigated inflammation (decreased the level of MUC1, p-NF-&#x3ba;B, IL-6 and TNF-&#x3b1;). Furthermore, in vitro assessments demonstrated that ISCs-EVs reduced apoptosis (P&#xa0;<&#xa0;0.01) and stimulated proliferation (P&#xa0;<&#xa0;0.05) of IEC-6&#xa0;cells, while enhancing mucin secretion in LS174T cells. In summary, our study provides a comprehensive assessment of the therapeutic effects of ISCs-EVs on NEC, using both animal and cell models. This highlights their potential for use in NEC treatment.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/39645054/