Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2023; 15(9): 908-930
Published online Sep 26, 2023. doi: 10.4252/wjsc.v15.i9.908
Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injury via the lung-gut axis
Lu Lv, En-Hai Cui, Bin Wang, Li-Qin Li, Feng Hua, Hua-Dong Lu, Na Chen, Wen-Yan Chen
Lu Lv, En-Hai Cui, Bin Wang, Feng Hua, Hua-Dong Lu, Na Chen, Wen-Yan Chen, Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, Huzhou 313000, Zhejiang Province, China
Li-Qin Li, Traditional Chinese Medicine Key Laboratory Cultivation Base of Zhejiang Province for the Development and Clinical Transformation of Immunomodulatory Drugs, Huzhou 313000, Zhejiang Province, China
Author contributions: Cui EH, Lv L, and Wang B conceived and designed the research; Lv L, Li LQ, and Lu HD acquired the data; Cui EH, Li LQ, and Hua F analyzed and interpreted the data; Lv L, Lu HD, Chen WY, and Chen N performed statistical analysis; Cui EH and Wang B obtained the funding; Lv L and Cui EH drafted the manuscript; Cui EH, Wang B, and Hua F revised the manuscript for important intellectual content; and all authors approved the final version of the article.
Supported by the Key Research and Development Project of Science and Technology Department of Zhejiang Province, No. 2019C03041.
Institutional review board statement: The study was reviewed and approved by the Animal Experimentation Ethics Committee of Zhejiang Eyong Pharmaceutical Research and Development Center (License No. SYXK(Zhe)2021-0033).
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Approval No. ZJEY-20220721-02).
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:
Corresponding author: En-Hai Cui, BM BCh, Doctor, Department of Respiratory and Critical Care Medicine, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, No. 1558 Third Ring North Road, Huzhou 313000, Zhejiang Province, China.
Received: May 12, 2023
Peer-review started: May 12, 2023
First decision: June 29, 2023
Revised: July 23, 2023
Accepted: September 6, 2023
Article in press: September 6, 2023
Published online: September 26, 2023
Research background

Acute lung injury (ALI) has high morbidity and mortality rates and needs effective treatment. Research has found that the gut microbiota improves lung injury through the lung-gut axis. Human umbilical cord mesenchymal cells (HUC-MSCs) can improve ALI.

Research motivation

Although HUC-MSCs can improve ALI, their biological mechanism of action is not yet clear.

Research objectives

To explore changes in the microbiota in the lung-gut axis and the relationship with HUC-MSC treatment.

Research methods

C57BL/6 mice were used to establish an ALI animal model by intraperitoneal injections of lipopolysaccharide. Wright’s staining, ELISA, hematoxylin-eosin staining, Evans blue dye leakage assay, immunohistochemistry, fluorescence in situ hybridization, and western blot were used to observe the improvement of ALI mice by HUC-MSCs. High-throughput 16S rDNA sequencing was used to observe the microbiota homeostases in the lung-gut axis. The non-targeted metabolomics was used to explore changes in lung tissue metabolites.

Research results

HUC-MSCs ameliorated histopathological damage in the lung and ileum of ALI mice. HUC-MSC treatment improved inflammation, endothelial barrier integrity, and bacterial translocation in the lungs and ileum of ALI mice. HUC-MSCs regulated lung-gut microbiota homeostasis. HUC-MSC treatment regulated the metabolic profile in the lung and ileum of ALI mice.

Research conclusions

This study shows the improvement of changes in the lung and ileum of ALI mice by HUC-MSCs, and suggests a correlation between HUM-MSC-improved ALI and gut and lung microbiota homeostases.

Research perspectives

This study explores the biological mechanism of HUC-MSCs in improving ALI from the perspective of the correlation between the microbiota in the lung-gut axis and lung tissue metabolites, providing a research basis for HUC-MSC treatment.