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World J Diabetes. Dec 15, 2022; 13(12): 1066-1095
Published online Dec 15, 2022. doi: 10.4239/wjd.v13.i12.1066
Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing
Jing Wu, Li-Hong Chen, Shi-Yi Sun, Yan Li, Xing-Wu Ran
Jing Wu, Li-Hong Chen, Shi-Yi Sun, Yan Li, Xing-Wu Ran, Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Ran XW and Chen LH designed the research study; Wu J, Sun SY and Li Y performed the literature retrieval; Wu J and Chen LH wrote the manuscript; Ran XW reviewed and revised the manuscript; All authors have read and approved the final manuscript.
Supported by the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University, No. ZYGD18025.
Conflict-of-interest statement: Authors declare no conflict of interests associated with this manuscript.
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 Non Commercial (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: Xing-Wu Ran, MD, Chief Physician, Professor, Innovation Center for Wound Repair, Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu 610041, Sichuan Province, China. ranxingwu@163.com
Received: September 29, 2022
Peer-review started: September 29, 2022
First decision: October 21, 2022
Revised: November 4, 2022
Accepted: November 23, 2022
Article in press: November 23, 2022
Published online: December 15, 2022
Processing time: 77 Days and 9.4 Hours
Abstract

Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.

Keywords: Diabetic wounds; Wound and injuries; Mesenchymal stem cells; Exosomes; Pre-conditioning; Preclinical translation

Core Tip: Diabetic chronic wounds (DCWs) are one of the most serious chronic complications of diabetes, and the efficacy of stem cell therapies for refractory chronic wounds has been studied previously. Stem cell-derived exosomes are one of the important active components of stem cell paracrine secretion, which inherit the wound repair capacity of parental cells as parts of novel cell-free therapies in addition to cell-bases ones. Herein we discuss the mechanism and latest progress of mesenchymal stem cell-derived exosomes in promoting DCW healing.