Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2020; 12(8): 879-896
Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.879
Role of mesenchymal stem cell derived extracellular vesicles in autoimmunity: A systematic review
Jing-Hua Wang, Xiao-Ling Liu, Jian-Mei Sun, Jing-Han Yang, Dong-Hua Xu, Shu-Shan Yan
Jing-Hua Wang, Jing-Han Yang, Clinical Medicine College, Weifang Medical University, Weifang 261000, Shandong Province, China
Xiao-Ling Liu, Department of Emergency Medicine, Yantai Shan Hospital, Yantai 264001, Shandong Province, China
Jian-Mei Sun, Department of Chemistry, School of Applied Chemistry, Food and Drug, Weifang Engineering Vocational College, Qingzhou 262500, Shandong Province, China
Dong-Hua Xu, Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Central Laboratory of the First Affiliated Hospital, Weifang 261000, Shandong Province, China
Shu-Shan Yan, Department of Gastrointestinal and Anal Diseases Surgery of the Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
Author contributions: All authors equally contributed to this work with regard to conception and design of the study, literature analysis, manuscript drafting, critical revision, and editing, and approval of the final version.
Supported by the Shandong Natural Science Foundation, No. ZR2019QH012.
Conflict-of-interest statement: The authors have no potential conflicts of interests to declare.
PRISMA 2009 Checklist statement: The guidelines of the PRISMA 2009 statement have been adopted.
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: Shu-Shan Yan, MD, Doctor, Department of Gastrointestinal and Anal Diseases Surgery, The Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China. yanshushan@163.com
Received: March 4, 2020
Peer-review started: March 4, 2020
First decision: April 25, 2020
Revised: July 2, 2020
Accepted: July 19, 2020
Article in press: July 19, 2020
Published online: August 26, 2020
Processing time: 175 Days and 3.3 Hours
ARTICLE HIGHLIGHTS
Research background

Mesenchymal stem cells (MSCs) have been reported to possess immune regulatory effects in innate and adaptive immune reactions. MSCs can mediate intercellular communications by releasing extracellular vesicles (EVs), which deliver functional molecules to targeted cells. MSC derived EVs (MSC-EVs) confer altering effects on many immune cells, including T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages. A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases. This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.

Research motivation

This article describes and focuses on the identification, characteristics, immunomodulatory function, and underlying mechanism of MSC-EVs in autoimmunity related diseases. Understanding the immunomodulation effects of MSC-EVs better will help us to investigate the pathogenesis of diseases and develop novel targeted medicines.

Research objectives

The immune modulation of MSC-EVs play a key role in disease initiation, maintenance, and progression. This article provides a new direction for us to understand the precise mechanisms of action of autoimmunity related diseases, which will promote the improvement of therapeutic regimen.

Research methods

Literature search was conducted in PubMed to retrieve articles published between 2010 and 2020 in the English language. The keywords, such as “MSCs,” “EVs,” “autoimmune responses,” “immune cells,” and “autoimmunity related diseases,” and Boolean operator “AND” and “NOT” coalesced admirably to be used for searching in vitro studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases. Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.

Research results

A large number of articles were retrieved and their abstracts were skimmed. When analyzing the publications, we found that it has been well documented that MSC-EVs have the ability to induce multiple immune cells, like T lymphocytes, B lymphocytes, natural killer cells, dendritic cells, and macrophages, to regulate immune responses in innate immunity and adaptive immunity. Many validated EVs-delivered molecules have been identified as key biomarkers, such as proteins, lipids, and nucleotides. Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.

Research conclusions

MSC-EVs play an important part in the differentiation, activation, and proliferation of immune cells, and they may become potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.

Research perspectives

MSC-EVs can serve as regulators in the pathogenesis of autoimmune related diseases. In particular, MSC-EVs and the encapsulated bioactive molecules are potential targets for the diagnosis and treatment of autoimmune disease, cancer, and other diseases. However, there is still a long way for investigating the therapeutic strategy for autoimmunity related diseases based on MSC-EVs. More in-depth research is warranted in the future, particularly regarding the molecular mechanism of MSC-EVs in autoimmunity