Intestinal stem cell-derived extracellular vesicles ameliorate necrotizing enterocolitis injury

Area of Science:

• Gastroenterology
• Regenerative Medicine
• Cell Biology

Background:

• Necrotizing enterocolitis (NEC) is a severe condition with limited therapeutic options.
• The therapeutic potential of intestinal stem cell-derived extracellular vesicles (ISCs-EVs) in NEC is largely unexplored.

Purpose of the Study:

• To investigate the therapeutic effects of ISCs-EVs on NEC.
• To evaluate ISCs-EVs' impact on intestinal healing, inflammation, and angiogenesis in NEC models.

Main Methods:

• Isolated Lgr5-positive intestinal stem cells (ISCs) and their derived extracellular vesicles (ISCs-EVs) from mice.
• Characterized ISCs-EVs using transmission electron microscopy, nanoparticle tracking analysis, and western blotting.
• Assessed ISCs-EVs' efficacy in a mouse model of NEC and in vitro cell cultures (IEC-6 and LS174T cells).

Main Results:

• ISCs-EVs treatment increased survival by over 20% in a mouse NEC model.
• Reduced intestinal damage by restoring crypts and decreasing MPO and cleaved-caspase 3 expression.
• Promoted angiogenesis (VEGF mRNA ~35% increase) and mitigated inflammation (reduced MUC1, p-NF-κB, IL-6, TNF-α).
• In vitro, ISCs-EVs reduced apoptosis (P < 0.01) and stimulated proliferation (P < 0.05) in IEC-6 cells, enhancing mucin secretion in LS174T cells.

Conclusions:

• ISCs-EVs demonstrate significant therapeutic potential for necrotizing enterocolitis.
• These findings support the further development of ISCs-EVs as a novel treatment strategy for NEC.