Published online Sep 26, 2020. doi: 10.4252/wjsc.v12.i9.922
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
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.
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.