Immunomodulatory effects of mesenchymal stromal cells-derived exosome

Abstract

The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors' bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1β, but increased the concentration of anti-inflammatory factor TGF-β during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.

Exosomes, your body’s answer to immune health

“…Thus, the lack of miR-223 within exosomes resulted in sepsis-induced heart failure, inflammation and death, while miR-223-containing exosomes attenuated the inflammatory response and minimized morality. These immune modulatory properties of MSC-derived exosomes are thus consistent with the findings by Chen et al (4).…”

“…Previous studies had shown that MSC-derived exosomes promoted cellular proliferation (5) and indoleamine 2,3-dioxygenase (IDO) activity, but this study reported that proliferation and IDO activity was unaffected (8). Additionally in this study (4), apoptosis was found to be upregulated in both PBMCs and CD3+ T cells but not in prior studies (8). It should be noted that these discrepancies might be due to the different components that are carried within different types of exosomes or the underlying complexity that differentiates MSCs from MSC-derived exosomes and thus may significantly affect biological activities.…”

“…These findings strongly support the immunomodulatory role of exosomes that originate from MSCs and their influence on host homeostasis. While the underlying mechanism(s) by which MSCs, exosomes and their secretory factors affect immunity is still lacking, Chen et al (4) examined the immunomodulatory properties that MSC-derived exosomes exert on peripheral blood mononuclear cells (PBMCs), with special emphasis on the T-lymphocyte immune subset.…”

“…Chen et al (4) found significant inhibition of the pro-inflammatory cytokines, IL1β and TNFα but enhancement of the expression of the antiinflammatory cytokine, TGFβ. This cytokine profile mimics the immunomodulatory effects of MSCs (5,6,9).…”

“…The key finding of Chen et al (4) was the role that MSC-derived exosomes play in dampening the activation of T-cells, enriching regulatory T-cell populations and their activity. The findings of their study further support the notion that MSC-derived exosomes can promote and maintain a modulated immune state.…”