Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2020; 12(7): 688-705
Published online Jul 26, 2020. doi: 10.4252/wjsc.v12.i7.688
Mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles: Potential roles in rheumatic diseases
Jing-Han Yang, Feng-Xia Liu, Jing-Hua Wang, Min Cheng, Shu-Feng Wang, Dong-Hua Xu
Jing-Han Yang, Jing-Hua Wang, Dong-Hua Xu, Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
Jing-Han Yang, Jing-Hua Wang, Dong-Hua Xu, Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
Feng-Xia Liu, Department of Allergy, Weifang People’s Hospital, Weifang 261000, Shandong Province, China
Min Cheng, Department of Physiology, Weifang Medical University, Weifang 261000, Shandong Province, China
Shu-Feng Wang, Medical Experimental Training Center, Weifang Medical University, Weifang 261000, Shandong Province, China
Author contributions: Yang JH collected the data and drafted this manuscript; Liu FX collected the data and revised the draft; Wang JH collected the data; Cheng M revised the Prisma 2009 and the references; Wang SF proposed some discussions in this work; Xu DH designed the systematic review and performed the data analysis; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81601408.
Conflict-of-interest statement: The authors have no potential conflicts of interests to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Dong-Hua Xu, MD, PhD, Doctor, Research Scientist, Central Laboratory of the First Affiliated Hospital and Department of Rheumatology of the First Affiliated Hospital, No. 2428 Yuhe Road, Kuiwen District, Weifang Medical University, Weifang 261000, Shandong Province, China. flower322@163.com
Received: March 4, 2020
Peer-review started: March 4, 2020
First decision: April 18, 2020
Revised: May 26, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 26, 2020
Processing time: 144 Days and 5.4 Hours
Abstract
BACKGROUND

Mesenchymal stem cells (MSCs) have been widely investigated in rheumatic disease due to their immunomodulatory and regenerative properties. Recently, mounting studies have implicated the therapeutic potency of MSCs mostly due to the bioactive factors they produce. Extracellular vesicles (EVs) derived from MSCs have been identified as a promising cell-free therapy due to low immunogenicity. Rheumatic disease, primarily including rheumatoid arthritis and osteoarthritis, is a group of diseases in which immune dysregulation and chronic progressive inflammation lead to irreversible joint damage. Targeting MSCs and MSC-derived EVs may be a more effective and promising therapeutic strategy for rheumatic diseases.

AIM

To evaluate the potential therapeutic effectiveness of MSCs and EVs generated from MSCs in rheumatic diseases.

METHODS

PubMed was searched for the relevant literature using corresponding search terms alone or in combination. Papers published in English language from January 1999 to February 2020 were considered. Preliminary screening of papers concerning analysis of "immunomodulatory function" or "regenerative function" by scrutinizing the titles and abstracts of the literature, excluded the papers not related to the subject of the article. Some other related studies were obtained by manually retrieving the reference lists of papers that comply with the selection criteria, and these studies were screened to meet the final selection and exclusion criteria.

RESULTS

Eighty-six papers were ultimately selected for analysis. After analysis of the literature, it was found that both MSCs and EVs generated from MSCs have great potential in multiple rheumatic diseases, such as rheumatoid arthritis and osteoarthritis, in repair and regeneration of tissues, inhibition of inflammatory response, and regulation of body immunity via promoting chondrogenesis, regulating innate and adaptive immune cells, and regulating the secretion of inflammatory factors. But EVs from MSCs exhibit much more advantages over MSCs, which may represent another promising cell-free restorative strategy. Targeting MSCs and MSC-derived EVs may be a more efficient treatment for patients with rheumatic diseases.

CONCLUSION

The enormous potential of MSCs and EVs from MSCs in immunomodulation and tissue regeneration offers a new idea for the treatment of rheumatism. However, more in-depth exploration is needed before their clinical application.

Keywords: Mesenchymal stem cell; Extracellular vesicle; Autoimmunity; Inflammation; Rheumatoid arthritis; Osteoarthritis

Core tip: Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) have long been thought to possess considerable immunomodulatory and regenerative potential. Rheumatic disease is a group of diseases marked by immune dysregulation and chronic progressive inflammation. Targeting MSCs and MSC-derived EVs may be a more efficient treatment for rheumatic diseases. However, before their application in the clinical treatment, a large number of preclinical studies and clinical studies are required to thoroughly assess their safety and efficiency. This work summarizes current advances and offers a strong basis for the next study of MSCs and MSC-derived EVs in this field.