Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes

Nojehdehi, Shahrzad; Soudi, Sara; Hesampour, Ardeshir; Rasouli, Shima; Soleimani, Masoud; Hashemi, Seyed Mahmoud

doi:10.1002/jcb.27260

Cited by 207 publications

(155 citation statements)

References 47 publications

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“…However, other studies have reported that SC-EVs inhibited the proliferation of NK cells and B cells, although its effect on the proliferation of T cells remains unclear (30,108). There are evidences that indicate that SC-EVs do not suppress T cell proliferation; however, they induce upregulation of Tregs and downregulation of pro-inflammatory cytokines (51,74,109).…”

Section: T Cellsmentioning

confidence: 99%

“…On the one hand, SC-EVs have been reported to induce the immune response of T helper type 1 (Th1) conversion to T helper type 2 (Th2). For example, SC-EVs drove the shift from Th1 toward Th2 cells and reestablished Th1/Th2 homeostasis by downregulating pro-inflammatory TNF-α and INF-γ and upregulating anti-inflammatory IL-10 or IL-4 (29,44,51,74,76) ( Table 1). Moreover, SC-EVs could also regulate Th2 immune response toward Th1.…”

Section: Stem Cell-derived Extracellular Vesicle Potentials In T Cellmentioning

confidence: 99%

“…cells, downregulation pro-inflammatory IL-17, promotion differentiation of Tregs (31,51,74,76,94) (Table 1) and CTLA-4+ Tregs (74), upregulation anti-inflammatory TGF-β, and inhibition aberrant inflammatory responses in stroke (31), type 1 diabetes (51,76), and chronic periodontitis (94). A possible underlying mechanism could be the immune equilibrium controlled by PGE2 and TGF-β (76) signaling pathways or miRNA-155-5p (94) in EVs.…”

Section: Sc-evs Regulate Th17/treg Balance Such As Inhibition the Difmentioning

confidence: 99%

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Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie

Wang²,

She

et al. 2020

Front. Immunol.

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Recent investigations on the regulatory action of extracellular vesicles (EVs) on immune cells in vitro and in vivo have sparked interest on the subject. As commonly known, EVs are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles containing exosomes, microvesicles, and apoptotic bodies. They are double-layer membrane-bound vesicles enriched with proteins, nucleic acids, and other active compounds. EVs are recognized as a novel apparatus for intercellular communication that acts through delivery of signal molecules. EVs are secreted by almost all cell types, including stem/progenitor cells. The EVs derived from stem/progenitor cells are analogous to the parental cells and inhibit or enhance immune response. This review aims to provide its readers a comprehensive overview of the possible mechanisms underlying the immunomodulatory effects exerted by stem/progenitor cell-derived EVs upon natural killer (NK) cells, dendritic cells (DCs), monocytes/macrophages, microglia, T cells, and B cells.

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Section: T Cellsmentioning

confidence: 99%

Section: Stem Cell-derived Extracellular Vesicle Potentials In T Cellmentioning

confidence: 99%

Section: Sc-evs Regulate Th17/treg Balance Such As Inhibition the Difmentioning

confidence: 99%

See 1 more Smart Citation

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie

Wang²,

She

et al. 2020

Front. Immunol.

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“…In a study using PBMC cells from type I diabetes patients, MSC-EV administration decreased Th17 response while increased Treg response [65]. Based on that, we differentiated lymphocytes to a pro-inflammatory condition (Th1) and as it was shown previously with MSCs treatment [66,67], a significant reduction of IFN-γ-secreting cells was observed after treatment with MSC-EVs. We then differentiated to another pro-inflammatory condition, Th17, but we did not see effect on T cell differentiation.…”

Section: Discussionmentioning

confidence: 69%

Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4+ T Lymphocytes Toward a Regulatory Profile

Cunha

Andrade-Oliveira²,

Almeida

et al. 2020

Cells

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Mesenchymal stromal cells (MSCs) can generate immunological tolerance due to their regulatory activity in many immune cells. Extracellular vesicles (EVs) release is a pivotal mechanism by which MSCs exert their actions. In this study, we evaluate whether mesenchymal stromal cell extracellular vesicles (MSC-EVs) can modulate T cell response. MSCs were expanded and EVs were obtained by differential ultracentrifugation of the supernatant. The incorporation of MSC-EVs by T cells was detected by confocal microscopy. Expression of surface markers was detected by flow cytometry or CytoFLEX and cytokines were detected by RT-PCR, FACS and confocal microscopy and a miRNA PCR array was performed. We demonstrated that MSC-EVs were incorporated by lymphocytes in vitro and decreased T cell proliferation and Th1 differentiation. Interestingly, in Th1 polarization, MSC-EVs increased Foxp3 expression and generated a subpopulation of IFN-γ + /Foxp3 + T cells with suppressive capacity. A differential expression profile of miRNAs in MSC-EVs-treated Th1 cells was seen, and also a modulation of one of their target genes, TGFbR2. MSC-EVs altered the metabolism of Th1-differentiated T cells, suggesting the involvement of the TGF-β pathway in this metabolic modulation. The addition of MSC-EVs in vivo, in an OVA immunization model, generated cells Foxp3 + . Thus, our findings suggest that MSC-EVs are able to specifically modulate activated T cells at an alternative regulatory profile by miRNAs and metabolism shifting.Cells 2020, 9, 1059 2 of 27 different biologic functions, which include, besides cell differentiation in multiple lines, tissue repair and immunosuppression. MSCs can modulate innate cells such as monocytes and macrophages, DCs and NK cells [3] and cells of the adaptive immune system, preventing the proliferation of CD4 + and CD8 + T cells and B cells. The effect of MSCs on T cells modulation is more widely studied. These cells suppress the proliferation of CD4 + and CD8 + naïve and memory T cells [4,5]. The presence of MSCs in lymphocyte culture may also lead to increase of regulatory T cell subpopulations (Treg) [6-9], a subtype essential for the suppression of immune response and tolerance induction [10]. Studies that pursue to identify the mechanisms by which MSCs exert their regulation suggest that the paracrine effect is more important than cell-cell contact, being the main mediator of this action [3]. In this context, the release of soluble factors with immunomodulatory properties, such as HGF [11], TGF-β [7], IL-10 [12], prostaglandin-E 2 (PGE 2 ) [13], indoleamine-2,3-dioxygenase (IDO) [14], has been identified as responsible for the effects of MSCs in several studies. Recently, nevertheless, the release of extracellular vesicles (EVs) by these cells has been demonstrated as an alternative mechanism by which MSCs perform their biologic effects [15].EVs include several particles which are classified according to their origin and size. Exosomes are small particles (40 to 100 nm in diameter), derived from the endocytic ...

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“…Exosomes isolated from MSCs can also be used in the treatment of T1D, as they are immunomodulatory and favour cell survival. Hence, treatment with hucMSCs exosomes improved pancreatic function in STZ‐treated mice by increasing the population of regulatory T cells and their anti‐inflammatory products IL‐4 and IL‐10 …”

Section: Exosomes As Therapy For Diabetesmentioning

confidence: 99%

Exosomes and diabetes

Castaño

Novials

Párrizas

2019

Diabetes Metabolism Res

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Summary Diabetes is a group of metabolic diseases characterized by elevated blood glucose levels that drive the development of life‐threatening complications. Diabetes results from a situation of insufficient insulin action, either by deficient production of the hormone by the pancreas, or by the development of insulin resistance in peripheral tissues such as liver, muscle, or the adipose depots. Communication between organs is thus central to the maintenance of glucose homoeostasis. Recently, several studies are evidencing that small vesicles called exosomes released by, amongst other, the adipose tissue can regulate gene expression in other tissues, hence modulating interorgan crosstalk. Therefore, exosomes participate in the development of diabetes and its associated complications. Their study holds the potential of providing us with novel biomarkers for the early diagnosis and stratification of patients at risk of developing diabetes, hence allowing the timely implementation of more personalized therapies. On the other hand, the molecular dissection of the pathways initiated by exosomes under situations of metabolic stress could help to gain a deeper knowledge of the pathophysiology of diabetes and its associated metabolic diseases.

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Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes

Cited by 207 publications

References 47 publications

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4+ T Lymphocytes Toward a Regulatory Profile

Exosomes and diabetes

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