Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy

BACKGROUND

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that affects premature infants. Although mounting evidence supports the therapeutic effect of exosomes on NEC, the underlying mechanisms remain unclear.

AIM

To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell (UCMSCs) exosomes, as well as their potential in alleviating NEC in neonatal mice.

METHODS

NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide (LPS), after which the mice received human UCMSC exosomes (hUCMSC-exos). The control mice were allowed to breastfeed with their dams. Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting. Colon tissues were collected from NEC neonates and analyzed by immunofluorescence. Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.

RESULTS

We found that autophagy is overactivated in intestinal epithelial cells during NEC, resulting in reduced expression of tight junction proteins and an increased inflammatory response. The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy. We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.

CONCLUSION

These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment. These findings also enhance our understanding of the role of the autophagy mechanism in NEC, offering potential avenues for identifying new therapeutic targets.

Key Words: Necrotizing enterocolitis, Autophagy, Umbilical cord mesenchymal stem cell, Exosomes, Intestinal epithelial cell, Intestinal barrier function

Core Tip: Based on observations of clinical samples, this study revealed a new mechanism by which human umbilical cord mesenchymal stem cells-derived exosomes reduce the inflammatory response and intestinal barrier dysfunction in neonatal mice with necrotizing enterocolitis (NEC) from the perspective of intestinal epithelial cell autophagy. These findings offer new insights for the clinical application of exosomes in NEC treatment and contribute to the establishment of a solid theoretical foundation.

• Citation: Zhu L, He L, Duan W, Yang B, Li N. Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy. World J Stem Cells 2024; 16(6): 728-738
• URL: https://www.wjgnet.com/1948-0210/full/v16/i6/728.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v16.i6.728