Immunomodulatory Properties of Mesenchymal Stromal Cells: An Update

Abstract

Mesenchymal stromal cells (MSCs) are characterized by an extraordinary capacity to modulate the phenotype and functional properties of various immune cells that play an essential role in the pathogenesis of inflammatory disorders. Thus, MSCs efficiently impair the phagocytic and antigen-presenting capacity of monocytes/macrophages and promote the expression of immunosuppressive molecules such as interleukin (IL)-10 and programmed cell death 1 ligand 1 by these cells. They also effectively inhibit the maturation of dendritic cells and their ability to produce proinflammatory cytokines and to stimulate potent T-cell responses. Furthermore, MSCs inhibit the generation and proinflammatory properties of CD4+ T helper (Th)1 and Th17 cells, while they promote the proliferation of regulatory T cells and their inhibitory capabilities. MSCs also impair the expansion, cytokine secretion, and cytotoxic activity of proinflammatory CD8+ T cells. Moreover, MSCs inhibit the differentiation, proliferation, and antibody secretion of B cells, and foster the generation of IL-10-producing regulatory B cells. Various cell membrane-associated and soluble molecules essentially contribute to these MSC-mediated effects on important cellular components of innate and adaptive immunity. Due to their immunosuppressive properties, MSCs have emerged as promising tools for the treatment of inflammatory disorders such as acute graft-versus-host disease, graft rejection in patients undergoing organ/cell transplantation, and autoimmune diseases.

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression

“…MSCs are known to display potent immunosuppressive and anti-inflammatory activities, modulating the activity of cells of innate and adaptative immune systems through a plethora of contact-dependent and independent mechanisms [ 191 ]. Together with their low immunogenicity [ 192 ], these features have granted their use in cellular therapy for the treatment of immunological disorders such as Graft-Versus-Host-Disease [ 193 ].…”

Catch me if you can: how AML and its niche escape immunotherapy

“…Mesenchymal stromal cells (MSCs) physiologically display a unique immune regulation ability by inhibiting/reprogramming the activation, proliferation, and function of both adaptive and innate immune cells, as extensively recently reviewed [50]. The role of MSCs in inhibiting innate and adaptive immunity in hematological malignancies, and in particular in AML, is under active investigation.…”

Therapeutic Implications of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Autoimmune Diseases: From Biology to Clinical Applications

“…Via interaction with dendritic cells, MSCs can induce the shift of CD4 + T cells with Th1 phenotype to cells with Th2 phenotype ( Figure 1 ) and this is accompanied by downregulation of proinflammatory cytokines such as IL-6, IFN-γ, and IL-17 and by concomitant upregulation of the anti-inflammatory cytokines IL-4 and IL-10 [ 48 , 49 ]. Indoleamine 2,3-dioxygenase (IDO), which is constitutively produced by MSCs and is also induced following ΙFN-γ stimulation, seems to mediate, at least in part, these effects [ 49 , 50 , 51 ] ( Figure 1 ). Additionally, via prostaglandin E2 (PGE2) secretion, MSCs suppress the differentiation of CD4 + T cells into Th17 cells and inhibit their function in vitro [ 52 ] ( Figure 1 ).…”