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

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%), 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%), and mitigated inflammation (decreased the level of MUC1, p-NF-κB, IL-6 and TNF-α). Furthermore, in vitro assessments demonstrated that ISCs-EVs reduced apoptosis (P<0.01) and stimulated proliferation (P<0.05) of IEC-6 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.
Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Le Zhang reports financial support was provided by Wuxi Health Committee. Le Zhang reports financial support was provided by Wuxi City People’s Government. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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