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

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.

Keywords: Endothelial Progenitor Cells; Mesenchymal Stem Cells; T cells; Immunosuppression; Immunoregulation; TNFα-TNFR2 signaling pathway

Core Tip: This present article aims to review for the first time some known similarities and differences between mesenchymal stem cell and endothelial progenitor cell immunomodulatory functions. It describes and compares different mechanisms that they use to suppress conventional T cells and/or to induce regulatory T cells. Among different mechanisms of action, we emphasize the implication of the immune checkpoint signaling pathways such as the tumor necrosis factor alpha-tumor necrosis factor receptor 2 axis. We try to cover the lack of information by proposing new research paths and their importance for future studies including in vitro and in vivo applications in regenerative medicine.