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World J Stem Cells. Sep 26, 2020; 12(9): 922-937
Published online Sep 26, 2020. doi: 10.4252/wjsc.v12.i9.922
Inflammatory niche: Mesenchymal stromal cell priming by soluble mediators
Aleksandra Jauković, Tamara Kukolj, Hristina Obradović, Ivana Okić-Đorđević, Slavko Mojsilović, Diana Bugarski
Aleksandra Jauković, Tamara Kukolj, Hristina Obradović, Ivana Okić-Đorđević, Slavko Mojsilović, Diana Bugarski, Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
Author contributions: Jauković A conceived of, designed, and wrote the manuscript; Kukolj T contributed to the article’s conception and writing; Obradović H performed the literature review and writing; Okić-Đorđević I contributed to the literature review and article writing; Mojsilović S performed the literature analysis and article editing; Bugarski D made critical revisions to the manuscript; all authors read and approved the final version of the manuscript.
Supported by the Ministry of Education, Science and Technological Development, Republic of Serbia, No. 451-03-68/2020-14/200015.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
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: Aleksandra Jauković, PhD, Associate Professor, Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Dr. Subotića 4, PO BOX 102, Belgrade 11129, Serbia. aleksandra@imi.bg.ac.rs
Received: April 14, 2020
Peer-review started: April 14, 2020
First decision: April 29, 2020
Revised: May 13, 2020
Accepted: September 1, 2020
Article in press: September 1, 2020
Published online: September 26, 2020
Processing time: 160 Days and 10.9 Hours
Abstract

Mesenchymal stromal/stem cells (MSCs) are adult stem cells of stromal origin that possess self-renewal capacity and the ability to differentiate into multiple mesodermal cell lineages. They play a critical role in tissue homeostasis and wound healing, as well as in regulating the inflammatory microenvironment through interactions with immune cells. Hence, MSCs have garnered great attention as promising candidates for tissue regeneration and cell therapy. Because the inflammatory niche plays a key role in triggering the reparative and immunomodulatory functions of MSCs, priming of MSCs with bioactive molecules has been proposed as a way to foster the therapeutic potential of these cells. In this paper, we review how soluble mediators of the inflammatory niche (cytokines and alarmins) influence the regenerative and immunomodulatory capacity of MSCs, highlighting the major advantages and concerns regarding the therapeutic potential of these inflammatory primed MSCs. The data summarized in this review may provide a significant starting point for future research on priming MSCs and establishing standardized methods for the application of preconditioned MSCs in cell therapy.

Keywords: Mesenchymal stem cells; Pro-inflammatory cytokines; Alarmins; Priming; Boosting the therapeutic potential

Core Tip: The inflammatory niche plays a key role in triggering the reparative and immunomodulatory functions of mesenchymal stromal/stem cells (MSCs). This paper summarizes the data on how soluble factors in the inflammatory microenvironment, including pro-inflammatory cytokines secreted by immune cells and alarmins released by damaged cells, affect MSCs’ ability to regenerate tissue and modulate the inflammatory response. We also analyze data from in vitro and in vivo studies, which highlight the influence of these factors on the therapeutic potential of MSCs, thus providing an important background for the development of preconditioning strategies that might improve the outcomes of MSC-based cell therapies.