Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Feb 26, 2021; 13(2): 177-192
Published online Feb 26, 2021. doi: 10.4252/wjSC.v13.i2.177
Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion
Hua-Su Zhu, Dong Li, Cong Li, Jin-Xian Huang, Shan-Shan Chen, Lan-Bo Li, Qing Shi, Xiu-Li Ju
Hua-Su Zhu, Cong Li, Jin-Xian Huang, Shan-Shan Chen, Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Dong Li, Qing Shi, Stem Cell and Regenerative Medicine Research Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Lan-Bo Li, Department of Animal Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong Province, China
Xiu-Li Ju, Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Zhu HS performed and supervised all the experiments, compiled and analyzed the results, drew the figures, conceived the manuscript, and contributed to all revision phases and writing of the text; Li D conceived the study, designed the experiments, interpreted the results, wrote the discussion, and contributed to the discussion of the draft and revised versions; Li C assisted with the mRNA isolation from animal tissues and gene expression experiments; Huang JX assisted with the Morris water maze experiments; Chen SS was responsible for histological examination and Western blot; Li LB contributed to the collection of blood samples from animals; Zhu HS, Li D, Shi Q, and Ju XL wrote the manuscript; all coauthors have reviewed and agreed the final manuscript.
Supported by Department of Science & Technology of Shandong Province, No. ZR2018MH012; Quancheng Industrial Leader Project, No. 2017018; and Ji'nan Science and Technology Development Foundation, No. 201704066.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee on Scientific Research of Shandong University Qilu Hospital.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals by the Ethics Committee on Animal Experiment of Shandong University Qilu Hospital (DWLL-2019-023, Shandong, China).
Conflict-of-interest statement: The authors report no conflict of interest.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiu-Li Ju, PhD, Doctor, Department of Pediatrics, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan 250012, Shandong Province, China. jxlqlyy@163.com
Received: July 31, 2020
Peer-review started: July 31, 2020
First decision: October 21, 2020
Revised: October 31, 2020
Accepted: November 11, 2020
Article in press: November 11, 2020
Published online: February 26, 2021
Processing time: 208 Days and 0.6 Hours
ARTICLE HIGHLIGHTS
Research background

Motion sickness (MS) is a disease that occurs during an unbalanced movement, and approximately 90% of people experience MS at least once in their lives. MS can present with gastrointestinal symptoms and activation of the autonomic nervous system. Additionally, it is accompanied by an increase in the levels of pro-inflammatory factors in the inner ear. However, the commonly used anti-inflammatory hormonal drugs have many side effects. Mesenchymal stem cells (MSCs) exert strong immunosuppressive effects and thus may serve as a therapeutic option for MS.

Research motivation

We can use the immunoregulatory properties of MSCs to suppress MS. Additionally, clarification of the molecular mechanisms underlying these properties may yield novel targets for the preventive treatment of MS.

Research objectives

In this study, we aimed to explore whether umbilical cord-derived MSCs (UC-MSCs) can suppress MS in a mouse model.

Research methods

UC-MSCs were cultured and phenotypically characterized. A total of 144 (equal numbers of males and females) 5wkold BALB/c mice were randomly divided into five groups, and UC-MSCs were infused into the tail veins of the MSCs group and MS + MSCs group. AS101-treated UC-MSCs were infused into the MS + AS101/MSCs group for prophylaxis. The mice were subjected to the Morris water maze test to experience MS and monitored for any sign of dizziness. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to assess the expression levels of inflammatory cytokines in the peripheral blood and petrous temporal bones of the mice. The petrous temporal bone samples were also histologically evaluated via hematoxylin-eosin (HE) staining. Additionally, Western blot analysis was performed to assess the cochlear levels of proteins involved in the JAK2/STAT3 signaling pathway.

Research results

Results of the Morris water maze test demonstrated that transplantation of UC-MSCs suppressed the symptoms of MS in mice. The UC-MSC-transplanted mice found the water maze platform faster than the MS group. The levels of interleukin-10 (IL-10) in the cochlear tissues were increased after transplantation with UC-MSCs, based on the ELISA and RT-qPCR results. Moreover, Western blot analysis showed that transplantation of UC-MSCs activated the JAK2/STAT3 signaling pathway in the cochlear tissues. These effects were abolished when the transplanted mice were treated with the IL-10 inhibitor AS101. Histologically, no obvious difference was observed among the petrous temporal bones of the mice in the five groups.

Research conclusions

Prophylactic transplantation of UC-MSCs can suppress MS in mice, particularly at 3-5 d after transplantation. This reduced sensitivity of the vestibular cortex to imbalance presumably results from improvement of the immune microenvironment by IL-10 secreted by UC-MSCs.

Research perspectives

In the future, we will explore additional MSC culture methods and cell-free administration of the MSC-derived active factors into mice. For example, we will culture MSCs in three dimensions (3D) to mimic their in vivo microenvironment, and administer MSC-derived exosomes to the oral or nasal mucosa. In this way, we hope to translate the anti-MS effect of MSCs to the clinic.