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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2020; 12(12): 1474-1491
Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1474
Novel insights for improving the therapeutic safety and efficiency of mesenchymal stromal cells
Mehdi Najar, Johanne Martel-Pelletier, Jean Pierre Pelletier, Hassan Fahmi
Mehdi Najar, Johanne Martel-Pelletier, Jean Pierre Pelletier, Hassan Fahmi, Department of Medicine, University of Montreal, Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC H2X 0A9, Canada
Author contributions: All authors provided intellectual contribution, and edited and approved the manuscript for publication in its present version.
Supported by La Chaire en Arthrose de l’Université de Montréal.
Conflict-of-interest statement: The authors declare no conflict of interests.
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: Mehdi Najar, PhD, Academic Fellow, Department of Medicine, University of Montreal, Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), 900 Saint-Denis Street, R Tower, 11th floor, Montreal, QC H2X 0A9, Canada. mnajar@ulb.ac.be
Received: June 23, 2020
Peer-review started: June 23, 2020
First decision: July 30, 2020
Revised: August 13, 2020
Accepted: September 25, 2020
Article in press: September 25, 2020
Published online: December 26, 2020
Processing time: 186 Days and 21.3 Hours
Abstract

Mesenchymal stromal cells (MSCs) have attracted great interest in the field of regenerative medicine. They can home to damaged tissue, where they can exert pro-regenerative and anti-inflammatory properties. These therapeutic effects involve the secretion of growth factors, cytokines, and chemokines. Moreover, the functions of MSCs could be mediated by extracellular vesicles (EVs) that shuttle various signaling messengers. Although preclinical studies and clinical trials have demonstrated promising therapeutic results, the efficiency and the safety of MSCs need to be improved. After transplantation, MSCs face harsh environmental conditions, which likely dampen their therapeutic efficacy. A possible strategy aiming to improve the survival and therapeutic functions of MSCs needs to be developed. The preconditioning of MSCs ex vivo would strength their capacities by preparing them to survive and to better function in this hostile environment. In this review, we will discuss several preconditioning approaches that may improve the therapeutic capacity of MSCs. As stated above, EVs can recapitulate the beneficial effects of MSCs and may help avoid many risks associated with cell transplantation. As a result, this novel type of cell-free therapy may be safer and more efficient than the whole cell product. We will, therefore, also discuss current knowledge regarding the therapeutic properties of MSC-derived EVs.

Keywords: Cell-therapy; Mesenchymal stromal cells; Safety; Extracellular vesicles; Efficiency; Preconditioning

Core Tip: Mesenchymal stromal cells (MSCs) have a strong capacity to regenerate injured tissues by displaying trophic and immunomodulatory functions. The tissue environment plays a significant role during the reparative process of MSCs. Preconditioning of MSCs with a specific signal promotes the adequate response. As the therapeutic functions of MSCs are mainly linked to their secretome, the use of extracellular vesicles as an acellular tool is strongly recommended. Thus, new insights on the properties of MSCs as well as their mechanisms of actions will help to develop a safe and efficient therapeutic strategy.