Stem Cell-Derived Extracellular Vesicles and Immune-Modulation

Abstract

Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.

The secretome of periodontal ligament stem cells from MS patients protects against EAE

“…Immunomodulatory cytokines present in EMVs of different MSCs has been reported in previous studies4549 In accord with these results, we noticed the presence of IL-10 and TGF-β in EMVs. Consequently, we suppose that the presence of IL-10 and TGF-β in both RR-MS patients and healthy donors EMVs may have crucial role in repressing the activation of pro-inflammatory signaling cascade in EAE mice.…”

Concise Review: MSC-Derived Exosomes for Cell-Free Therapy

“…MSC-derived exosomes are also immunologically active based on evidence that they suppressed proliferation and IFN-g secretion by T cells stimulated with anti-CD3 and anti-CD28 antibodies [77], and also enhanced the survival of allogenic skin grafts in mice by enhancing T cell polarization to a regulatory phenotype [78]. A growing number of studies suggest that MSC-derived exosomes mimic the ability of MSCs to influence the activity of immune effector cells including B, T, NK, dendritic cells, and macrophages although not all studies show positive effects [reviewed in [79]]. Collectively, these studies readily demonstrate that MSC-derived exosomes recapitulate to a large extent the immensely broad therapeutic effects previously attributed to MSCs.…”

Nexus between extracellular vesicles, immunomodulation and tissue remodeling: for good or for bad?

“…An example could be seen in the down-regulation of NK and B-cell proliferation by inflammatory cytokines (21). It is anticipated that a pro-inflammatory environment could not only modify the composition of EVs but also the consequent biological activities of immune effector cells, with possibility of increased risks of unpredictable effects (14).…”

“…The immunomodulatory and inflammatory roles of EVs have recently been suggested in huge body of evidence (12)(13)(14)(15). The most profound aspect of EVs elicited in triggering immune responses or provoking pro-inflammatory responses owe greatly to the presence of MHC-I and -II complexes.…”