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      Differences and similarities between mesenchymal stem cell and endothelial progenitor cell immunoregulatory properties against T cells

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          Abstract

          Bone-marrow-derived mesenchymal stem cells and endothelial progenitor cells have some interesting biological properties that make them unique for cell therapy of degenerative and cardiovascular disorders. Although both cell populations have been already studied and used for their regenerative potentials, recently their special immunoregulatory features have brought much more attention. Mesenchymal stem cells and endothelial progenitor cells have both proangiogenic functions and have been shown to suppress the immune response, particularly T cell proliferation, activation, and cytokine production. This makes them suitable choices for allogeneic stem cell transplantation. Nevertheless, these two cells do not have equal immunoregulatory activities. Many elements including their extraction sources, age/passage, expression of different markers, secretion of bioactive mediators, and some others could change the efficiency of their immunosuppressive function. However, to our knowledge, no publication has yet compared mesenchymal stem cells and endothelial progenitor cells for their immunological interaction with T cells. This review aims to specifically compare the immunoregulatory effect of these two populations including their T cell suppression, deactivation, cytokine production, and regulatory T cells induction capacities. Moreover, it evaluates the implications of the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis as an emerging immune checkpoint signaling pathway controlling most of their immunological properties.

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          Most cited references120

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          Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.

          Apoptosis induced by TNF-receptor I (TNFR1) is thought to proceed via recruitment of the adaptor FADD and caspase-8 to the receptor complex. TNFR1 signaling is also known to activate the transcription factor NF-kappa B and promote survival. The mechanism by which this decision between cell death and survival is arbitrated is not clear. We report that TNFR1-induced apoptosis involves two sequential signaling complexes. The initial plasma membrane bound complex (complex I) consists of TNFR1, the adaptor TRADD, the kinase RIP1, and TRAF2 and rapidly signals activation of NF-kappa B. In a second step, TRADD and RIP1 associate with FADD and caspase-8, forming a cytoplasmic complex (complex II). When NF-kappa B is activated by complex I, complex II harbors the caspase-8 inhibitor FLIP(L) and the cell survives. Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated.
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            Control of regulatory T cell development by the transcription factor Foxp3.

            Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.
              • Record: found
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              • Article: found
              Is Open Access

              Mesenchymal stem cell perspective: cell biology to clinical progress

              The terms MSC and MSCs have become the preferred acronym to describe a cell and a cell population of multipotential stem/progenitor cells commonly referred to as mesenchymal stem cells, multipotential stromal cells, mesenchymal stromal cells, and mesenchymal progenitor cells. The MSCs can differentiate to important lineages under defined conditions in vitro and in limited situations after implantation in vivo. MSCs were isolated and described about 30 years ago and now there are over 55,000 publications on MSCs readily available. Here, we have focused on human MSCs whenever possible. The MSCs have broad anti-inflammatory and immune-modulatory properties. At present, these provide the greatest focus of human MSCs in clinical testing; however, the properties of cultured MSCs in vitro suggest they can have broader applications. The medical utility of MSCs continues to be investigated in over 950 clinical trials. There has been much progress in understanding MSCs over the years, and there is a strong foundation for future scientific research and clinical applications, but also some important questions remain to be answered. Developing further methods to understand and unlock MSC potential through intracellular and intercellular signaling, biomedical engineering, delivery methods and patient selection should all provide substantial advancements in the coming years and greater clinical opportunities. The expansive and growing field of MSC research is teaching us basic human cell biology as well as how to use this type of cell for cellular therapy in a variety of clinical settings, and while much promise is evident, careful new work is still needed.

                Author and article information

                Contributors
                Journal
                World J Stem Cells
                WJSC
                World Journal of Stem Cells
                Baishideng Publishing Group Inc
                1948-0210
                26 August 2021
                26 August 2021
                : 13
                : 8
                : 971-984
                Affiliations
                Institut national de la santé et de la recherche médicale (Inserm) Unité Mixte de Recherche-Inserm-Ministère de la Défense 1197, Hôpital Paul Brousse, Villejuif 94800, France
                Microenvironment & Immunity Unit, Institut Pasteur, Paris 75724, France
                Institut national de la santé et de la recherche médicale (Inserm) Unit 1224, Paris 75724, France
                Department of Pharmacognosy, University of Vienna, Vienna 1090, Austria
                Institut national de la santé et de la recherche médicale (Inserm) Unité Mixte de Recherche-Inserm-Ministère de la Défense 1197, Hôpital Paul Brousse, Villejuif 94800, France
                Paris-Saclay University, Villejuif 94800, France
                Institut national de la santé et de la recherche médicale (Inserm) Unité Mixte de Recherche-Inserm-Ministère de la Défense 1197, Hôpital Paul Brousse, Villejuif 94800, France
                Paris-Saclay University, Villejuif 94800, France
                CellMedEx; Saint Maur Des Fossés 94100, France
                Institut national de la santé et de la recherche médicale (Inserm) Unité Mixte de Recherche-Inserm-Ministère de la Défense 1197, Hôpital Paul Brousse, Villejuif 94800, France
                Paris-Saclay University, Villejuif 94800, France
                CellMedEx; Saint Maur Des Fossés 94100, France. sina.naserian@ 123456inserm.fr
                Author notes

                Author contributions: Razazian M and Khosravi M contributed equally in this study; Naserian S conceived the subject and determined the different sections of the manuscript; Razazian M, Khosravi M, Bahiraii S, Shamdani S, and Naserian S wrote the manuscript; Uzan G, Shamdani S, and Naserian S revised the manuscript; All authors read and approved the final manuscript.

                Corresponding author: Sina Naserian, PhD, Director, Research Scientist, Institut national de la santé et de la recherche médicale (Inserm) Unité Mixte de Recherche-Inserm-Ministère de la Défense 1197, Hôpital Paul Brousse, Bâtiment Lavoisier, 12-14 avenue Paul Vaillant Couturier, Villejuif 94800, France. sina.naserian@ 123456inserm.fr

                Article
                jWJSC.v13.i8.pg971
                10.4252/wjsc.v13.i8.971
                8422932
                34567420
                fe55e7e0-a2b4-4b23-8e23-b9c466c2ff19
                ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

                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 Non-Commercial (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/

                History
                : 24 February 2021
                : 28 April 2021
                : 16 July 2021
                Categories
                Review

                endothelial progenitor cells,mesenchymal stem cells,t cells,immunosuppression,immunoregulation,tnfα-tnfr2 signaling pathway

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