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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2020; 12(9): 966-985
Published online Sep 26, 2020. doi: 10.4252/wjsc.v12.i9.966
Senescent mesenchymal stem/stromal cells and restoring their cellular functions
Qing-Shu Meng, Jing Liu, Lu Wei, Hui-Min Fan, Xiao-Hui Zhou, Xiao-Ting Liang
Qing-Shu Meng, Jing Liu, Lu Wei, Hui-Min Fan, Xiao-Hui Zhou, Xiao-Ting Liang, Shanghai Heart Failure Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Qing-Shu Meng, Jing Liu, Lu Wei, Hui-Min Fan, Xiao-Hui Zhou, Xiao-Ting Liang, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Qing-Shu Meng, Jing Liu, Lu Wei, Hui-Min Fan, Xiao-Hui Zhou, Xiao-Ting Liang, Institute of Integrated Traditional Chinese and Western Medicine for Cardiovascular Chronic Diseases, Tongji University School of Medicine, Shanghai 200120, China
Hui-Min Fan, Department of Heart Failure, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Xiao-Ting Liang, Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200120, China
Author contributions: Meng QS and Liu J contributed equally to this work; Liang XT and Meng QS defined the study topic; Liu J, Wei L, and Fan HM collected the references; Meng QS wrote the paper; Liu J made the tables; Liang XT and Zhou XH revised the manuscript and resolved all disagreements in discussion with Meng QS and Liu J.
Supported by the National Natural Science Foundation of China, Nos. 81500207, 81670458, and 81470393; Shanghai Municipal Health and Family Planning Commission, No. ZY(2018-2020)-FWTX-2007; Shanghai Key Medical Discipline for Critical Care Medicine, No. 2017zz02017; the National Key Research and Development Program of China, No. 2017YFA0105600; Major Program of Development Fund for Shanghai Zhangjiang National Innovtaion Demonstration Zone < Stem Cell Strategic Biobank and Stem Cell Clinical Technology Transformation Platform>, No. ZJ2018-ZD-004; the Science and Technology Commission of Shanghai Municipality, No. 17431906600; and the Top-level Clinical Discipline Project of Shanghai Pudong, No. PWYgf2018-05.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this work.
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: Xiao-Ting Liang, MD, PhD, Research Fellow, Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, No. 150, Jimo Road, Shanghai 200120, China. liangxt@tongji.edu.cn
Received: May 27, 2020
Peer-review started: May 27, 2020
First decision: June 15, 2020
Revised: June 23, 2020
Accepted: July 19, 2020
Article in press: July 19, 2020
Published online: September 26, 2020
Abstract

Mesenchymal stem/stromal cells (MSCs) have various properties that make them promising candidates for stem cell-based therapies in clinical settings. These include self-renewal, multilineage differentiation, and immunoregulation. However, recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products. Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs. This review will summarize the current knowledge on characteristics and functional changes of aged MSCs. Additionally, it will highlight cell rejuvenation strategies such as molecular regulation, non-coding RNA modifications, and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.

Keywords: Mesenchymal stem cells, Senescence, Features, Function, Rejuvenation strategy

Core Tip: Mesenchymal stem cell (MSC) administration is a promising therapeutic strategy for various human diseases. However, cell aging limits MSC function and therapeutic properties via reducing their activities. We review the morphological changes, molecular expression alterations, and functional degeneration of aged MSCs, and the effects of aged MSCs on immune cells and other target cells. Additionally, we summarize the strategies to rejuvenate aged MSCs to enhance their clinical potential.