Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

Abstract

Due to the great therapeutic interest that involves the translation of mesenchymal stromal cells (MSCs) into clinical practice, they have been widely studied as innovative drugs, in order to treat multiple pathologies. MSC-based cell therapy involves the administration of MSCs either locally or systemically into the receptor body where they can traffic and migrate towards the affected tissue and participate in the process of healing. The therapeutic effects of MSCs compromise of different mechanisms such as the functional integration of differentiated MSCs into diseased host tissue after transplantation, their paracrine support, and their impact on the regulation of both the innate and the acquired immune system. Here, we establish and provide recent advances about the principal mechanisms of action through which MSCs can perform their activity and effect as a therapeutic tool. The purpose of this review is to examine and discuss the MSCs capacity of migration, their paracrine effect, as well as MSC-mediated modifications on immune cell responses.

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

“…However, it should be borne in mind that the direct effectors are still unclear, but it seems that the secretome of MSCs play an crucial role in suppression of tumors [64]. It should be stressed that various molecular mechanisms seem to be involved in therapeutic MSC actions in vivo and increase their regenerative potential [65]. Among others, direct MSC differentiation into cardiac and endothelial cells and the paracrine activity mediated by MSC-derived soluble molecules and vesicles are currently considered as major factors mediating beneficial effects of MSC-based therapies in various viable diseases [65][66][67][68][69].…”

“…It should be stressed that various molecular mechanisms seem to be involved in therapeutic MSC actions in vivo and increase their regenerative potential [65]. Among others, direct MSC differentiation into cardiac and endothelial cells and the paracrine activity mediated by MSC-derived soluble molecules and vesicles are currently considered as major factors mediating beneficial effects of MSC-based therapies in various viable diseases [65][66][67][68][69]. However, recent studies showed that paracrine function of MSCs is the main mechanism by which these cells participate in tissue repair [68].…”

Application of autologous endometrial mesenchymal stromal/stem cells increases thin endometrium receptivity: a case report

“…The use of MSCs in regenerative medicine has gained increasing popularity in recent years due to outstanding therapeutic potential of this cell type. They stimulate the organism's regenerative capacity in exerting a paracrine effect, producing cytokines and growth factors and thus pushing the on-site stem/progenitor cells and recruiting stem cells from other locations; besides, they are able to integrate into the damaged area [2].…”

Dental follicle stem cells rescue the regenerative capacity of inflamed rat dental pulp through a paracrine pathway

“…On the one hand, MSCs exert immunosuppressive effects by suppressing the secretion of proinflammatory factors while increasing the expression of anti-inflammatory mediators of immune cells [9,10], and on the other hand, MSCs regulate immune responses by eliciting the reprogramming of macrophages, suppressing the activation of B and T cells, and facilitating the proliferation of Treg cells [6,7,11,12]. Based on their immunomodulatory capacities, MSCs are prospective candidates for use in cellbased therapies for various immune and inflammatory diseases [13][14][15], but the application of these therapies is limited by difficulty in acquiring MSCs.…”