Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

Abstract

Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed. Under inflammatory conditions, MSCs-derived factors suppress both innate and adaptive immunity by attenuating maturation and capacity for antigen presentation of dendritic cells, by inducing polarization of macrophages towards alternative phenotype, by inhibiting activation and proliferation of T and B lymphocytes and by reducing cytotoxicity of NK and NKT cells. In this review, we emphasized current findings regarding immuno-modulatory effects of MSC-derived factors and emphasize their potential in the therapy of immune-mediated diseases. © 2017 BioFactors, 43(5):633-644, 2017.

The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration

“…IL‐1Ra regulates TLR‐4 signaling pathway in MSCs, leucocytes, and nonimmune cells, having important role in the modulation of immune response against bacterial antigens and allergens in the lungs . The effects of MSC‐derived IL‐1Ra on TLR‐4 axis depend on the role that TLR‐4‐expressing cells play in the immune response to the inhaled antigens . During the onset of bacterial pneumonia, under the influence of low concentration of inflammatory cytokines, MSCs obtain proinflammatory phenotype and cooperate with lung resident immune cells (macrophages, DCs) in the elimination of bacterial pathogens .…”

“…MSC‐derived IL‐1Ra regulates ILC2‐driven immune response in the lungs by suppressing TLR‐4‐signaling in AECs . Through the production of IL‐1Ra, MSCs attenuate TLR‐4:IL‐1α‐dependent release of alarmins in injured AECs and inhibit generation and expansion of ILC2 …”

“…CD4 + Th2 cells, in similar manner as ILC2, induce activation of mast cells, basophils, and eosinophils in the lungs and promote progression of chronic airway inflammation . By suppressing TLR‐4:IL‐1α signaling pathway in lung DCs, MSC‐derived IL‐1Ra reduces DCs migration to the draining lymph nodes, prevents generation of CD4 + Th2 cells, and attenuates IL‐4‐, IL‐5‐, and IL‐13‐driven inflammation in the lungs . Accordingly, significantly reduced number of activated HDM‐loaded DCs were observed in the mediastinal lymph nodes of MSC‐treated animals .…”

“…11 Among MSC-sourced factors, TGF-β, nitric oxide, indolamine 2,3-dioxygenase, IL-10, IL-6, leukocyte inhibitory factor, prostaglandin E2 (PGE2), and IL-1 receptor antagonist (IL-1Ra) have been mainly attributed to the beneficial effects of MSCs in attenuation of acute and chronic inflammation. 12 Herewith, we summarized current knowledge regarding the therapeutic potential of MSC-derived IL-1Ra in attenuation of organ-specific and systemic inflammatory diseases. An extensive literature review was carried out in June 2019 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present.…”

Issue Highlights

“…The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors. MSC‐derived factors attenuate maturation and capacity for antigen presentation of dendritic cells, induce polarization of macrophages towards alternative phenotype, reduce cytotoxicity of natural killer (NK) and NKT cells and suppress activation and proliferation of T and B lymphocytes .…”