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. • ISCs-Exo inhibits neutrophil infiltration in the terminal ileum of NEC mice. • ISCs-Exo reduces the expression of pro-inflammatory cytokines in NEC mice. • ISCs-Exo can increase the number and activity of goblet cells. • ISCs-Exo enhance the recovery of intestinal barrier function in NEC neonatal mice.