Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2023; 15(3): 52-70
Published online Mar 26, 2023. doi: 10.4252/wjsc.v15.i3.52
Immunomodulation: The next target of mesenchymal stem cell-derived exosomes in the context of ischemic stroke
Xiao-Qian Shan, Yong-Yin Luo, Jun Chang, Jing-Jing Song, Nan Hao, Lan Zhao
Xiao-Qian Shan, Yong-Yin Luo, Jun Chang, Jing-Jing Song, Nan Hao, Lan Zhao, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
Xiao-Qian Shan, Yong-Yin Luo, Jun Chang, Jing-Jing Song, Nan Hao, Lan Zhao, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
Author contributions: Shan XQ was responsible for conceptualization, wrote the review and editing; Luo YY, Chang J, Song JJ and Hao N prepared for the original draft; Zhao L was responsible for the supervision; All authors have contributed to the article and approved the submitted version.
Supported by National Natural Science Foundation of China, No. 82074533.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Lan Zhao, PhD, Research Fellow, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88 Chang Ling Road, Xi Qing District, Tianjin 300381, China. lanzhao69@163.com
Received: December 26, 2022
Peer-review started: December 26, 2022
First decision: January 6, 2023
Revised: January 19, 2023
Accepted: February 27, 2023
Article in press: February 27, 2023
Published online: March 26, 2023
Abstract

Ischemic stroke (IS) is the most prevalent form of brain disease, characterized by high morbidity, disability, and mortality. However, there is still a lack of ideal prevention and treatment measures in clinical practice. Notably, the transplantation therapy of mesenchymal stem cells (MSCs) has been a hot research topic in stroke. Nevertheless, there are risks associated with this cell therapy, including tumor formation, coagulation dysfunction, and vascular occlusion. Also, a growing number of studies suggest that the therapeutic effect after transplantation of MSCs is mainly attributed to MSC-derived exosomes (MSC-Exos). And this cell-free mediated therapy appears to circumvent many risks and difficulties when compared to cell therapy, and it may be the most promising new strategy for treating stroke as stem cell replacement therapy. Studies suggest that suppressing inflammation via modulation of the immune response is an additional treatment option for IS. Intriguingly, MSC-Exos mediates the inflammatory immune response following IS by modulating the central nervous system, the peripheral immune system, and immunomodulatory molecules, thereby promoting neurofunctional recovery after stroke. Thus, this paper reviews the role, potential mechanisms, and therapeutic potential of MSC-Exos in post-IS inflammation in order to identify new research targets.

Keywords: Mesenchymal stem cells, Exosomes, Ischemic stroke, Immunomodulation, Inflammation, Exosome therapy

Core Tip: Mesenchymal stem cell-derived exosomes (MSC-Exos) are an emerging strategy for treating ischemic stroke (IS) and have demonstrated certain achievements in animal studies. Here, we review and discuss the mechanisms of MSC-Exos in treating IS through immunomodulation, the current responses to the clinical limitations of MSC-Exos therapy, and the issues that need to be addressed in future MSC-Exos research.