Abstract
Mesenchymal stem/stromal cells (MSCs) have an immunoregulatory capacity and have been used in different clinical protocols requiring control of the immune response. However, variable results have been obtained, mainly due to the effect of the microenvironment on the induction, increase, and maintenance of MSC immunoregulatory mechanisms. In addition, the importance of cell–cell contact for MSCs to efficiently modulate the immune response has recently been highlighted. Because these interactions would be difficult to achieve in the physiological context, the release of extracellular vesicles (EVs) and their participation as intermediaries of communication between MSCs and immune cells becomes relevant. Therefore, this article focuses on analyzing immunoregulatory mechanisms mediated by cell contact, highlighting the importance of intercellular adhesion molecule-1 (ICAM-1) and the participation of EVs. Moreover, the effects of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), the main cytokines involved in MSC activation, are examined. These cytokines, when used at the appropriate concentrations and times, would promote increases in the expression of immunoregulatory molecules in the cell and allow the acquisition of EVs enriched with these molecules. The establishment of certain in vitro activation guidelines will facilitate the design of conditioning protocols to obtain functional MSCs or EVs in different pathophysiological conditions.
Highlights
Immunology and Stem Cells Laboratory, Multidisciplinary Unit of Experimental Research Zaragoza, Citation: López-García, L.; Castro-Manrreza, M.E
Exposure of AT-Mesenchymal stem/stromal cells (MSCs) to the plasma of patients with acute graft-versus-host disease (GVHD). Increased their ability to induce Treg differentiation in vitro [134]. These results reveal the importance of the design of in vitro conditioning strategies that ensure the therapeutic success of these cells under different pathophysiological conditions
An immediate increase in programmed cell death ligand 1 (PD-L1)+ exosomes was observed in the plasma of patients with acute GVHD who were treated with clinical-grade Wharton’s jelly-derived MSCs (WJ-MSCs), which decreased as time progressed (1–8 h) [106]. These results indicate that these structures can affect the function of their target cells through PD-L1, which highlights the importance of the mechanisms involving cell–cell contact
Summary
MSCs generate an anti-inflammatory environment by modulating the function of immune cells, such as neutrophils, natural killer (NK) cells, monocytes, macrophages, dendritic cells (DCs), and T and B lymphocytes [7,8,9,10,11,12,13]. It is currently proposed that MSCs modulate the activation, differentiation, and effector function of immune cells by secreting factors through cell–cell contact and extracellular vesicles (Figure 1). The activation of MSCs is induced by inflammatory cytokines such as tumor necrosis factor-alpha (TNFα), interferon-gamma (IFN-γ), interleukin (IL)-1, and IL-17 [8,9,10,11,12,13,14]. Because TNF-α and IFN-γ are the first cytokines secreted in an inflammatory response, it is relevant to analyze their effects on the expression of molecules involved in the different immunoregulatory mechanisms used by MSCs (Figure 1)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
