Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2024; 16(6): 728-738
Published online Jun 26, 2024. doi: 10.4252/wjsc.v16.i6.728
Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy
Lin Zhu, Lu He, Wu Duan, Bo Yang, Ning Li
Lin Zhu, Lu He, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Hubei Province, China
Wu Duan, Division of Endocrinology, Department of Internal Medicine, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Wu Duan, Shenzhen Research Institute of Shandong University, Shenzhen 518000, Guangdong Province, China
Bo Yang, Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Hubei Province, China
Ning Li, Department of Physical Education, Heze University, Heze 274015, Shandong Province, China
Co-corresponding authors: Bo Yang and Ning Li.
Author contributions: Zhu L and Li N designed and coordinated the study; Zhu L, He L, and Duan W performed the experiments, acquired and analyzed data; Zhu L wrote the manuscript; Li N and Yang B contributed to the editing, polishing, and data processing of this manuscript. Li N and Yang B contributed equally as corresponding author, and all authors approved the final version of the article.
Supported by China International Medical Foundation, No. Z-2019-41-2101-04; China Postdoctoral Science Foundation Funded Project, No. 2022M721957; West China Psychiatric Association, No. WL2022102; and Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515110717.
Institutional review board statement: The study was reviewed and approved by the ethical standards of Qilu Hospital of Shandong University ethics committee (KYLL-202311-036-1). It was performed in accordance with the International Ethical Guidelines for Human Biomedical Research (2012). The information regarding the patients with NEC was provided by the guardians of the patients. Written informed consent was obtained from participants involved in the study.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (license No. SYXK20230003).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ning Li, Doctor, Department of Physical Education, Heze University, No. 2269 Daxue Road, Mudan District, Heze 274015, Shandong Province, China. hzlqlm@163.com
Received: January 26, 2024
Revised: March 17, 2024
Accepted: April 19, 2024
Published online: June 26, 2024
Processing time: 150 Days and 23.9 Hours
Abstract
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.

Keywords: 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.