Extracellular Vesicles as Therapeutic Agents in Systemic Lupus Erythematosus

Perez-Hernandez, Javier; Redón, Josep; Cortés, Raquel

doi:10.3390/ijms18040717

Cited by 50 publications

(35 citation statements)

References 89 publications

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“…48 On the other hand, ameliorative effect of treatment with exosomes derived from MSCs in different autoimmune experimental models including osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis in concordance with the results of the current study may be indicative of the importance of different sources of exosomes and even the source of the MSCs, and the importance of dominant microenvironment. 49,50…”

Section: Discussionmentioning

confidence: 99%

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

Nojehdehi

Soudi

Hesampour

et al. 2018

J of Cellular Biochemistry

208

142

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Exosomes derived from adipose tissue-derived mesenchymal stem cells (AD-MSCs) have immunomodulatory effects of T-cell inflammatory response and reduction of clinical symptoms on streptozotocin-induced of the type-1 diabetes mellitus (T1DM). Beside control group and untreated T1DM mice, a group of T1DM mice was treated with intraperitoneal injections of characterized exosomes derived from autologous AD-MSCs. Body weight and blood glucose levels were measured during the procedure. Histopathology and immunohistochemistry were used for evaluation of pancreatic islets using hemotoxylin and eosin (H&E) staining and anti-insulin antibody. Isolated splenic mononuclear cells (MNCs) were subjected to splenocytes proliferation assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, immunophenotyping of regulatory T cells and cytokines. A significant increase in the levels of interleukin-4 (IL-4), IL-10, and transforming growth factor-β, and a decrease in the levels of IL-17 and interferon-γ in concordance with the significant increase in the Treg cell ratio in splenic MNCs (P < 0.05) was shown in T1DM mice treated with AD-MSC's exosomes as compared to T1DM untreated mice. This amelioration of autoimmune reaction after treatment of T1DM mice with the AD-MSC exosomes was confirmed with a significant increase in islets using H&E staining and Immunohistochemistry analyses. As expected, body weight, blood glucose levels in a survival of T1DM mice treated with AD-MSC's exosomes were maintained stable in comparison to untreated T1DM mice. It can be concluded that AD-MSC's exosomes exert ameliorative effects on autoimmune T1DM through increasing regulatory T-cell population and their products without a change in the proliferation index of lymphocytes, which makes them more effective and practical candidates.

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Section: Discussionmentioning

confidence: 99%

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

Nojehdehi

Soudi

Hesampour

et al. 2018

J of Cellular Biochemistry

208

142

View full text Add to dashboard Cite

show abstract

“…SLE is an immune complex disease where disease symptoms arise due to the reduced clearance of immune complexes, which leads to complement-mediated inflammation. EVs also associate with immunoglobulins and enhance the formation of such pathological immune complexes in SLE [ 54 ]. A recent study showed that distinct subpopulations of EVs harboring immunoglobulins were associated with distinct clinical characteristics of SLE and may therefore serve as biomarkers in future [ 55 ].…”

Section: Evs and The Blood Plasmamentioning

confidence: 99%

Molecular interactions at the surface of extracellular vesicles

et al. 2018

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Extracellular vesicles such as exosomes, microvesicles, apoptotic bodies, and large oncosomes have been shown to participate in a wide variety of biological processes and are currently under intense investigation in many different fields of biomedicine. One of the key features of extracellular vesicles is that they have relatively large surface compared to their volume. Some extracellular vesicle surface molecules are shared with those of the plasma membrane of the releasing cell, while other molecules are characteristic for extracellular vesicular surfaces. Besides proteins, lipids, glycans, and nucleic acids are also players of extracellular vesicle surface interactions. Being secreted and present in high number in biological samples, collectively extracellular vesicles represent a uniquely large interactive surface area which can establish contacts both with cells and with molecules in the extracellular microenvironment. Here, we provide a brief overview of known components of the extracellular vesicle surface interactome and highlight some already established roles of the extracellular vesicle surface interactions in different biological processes in health and disease.

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“…Exosome and microvesicles are emerging as novel therapeutic targets in treatment of disease as they have been shown to contribute to inflammatory processes ( Foers et al, 2017 ) and the progression of numerous pathologies including autoimmune diseases ( Antwi-Baffour et al, 2010 ; Withrow et al, 2016 ; Perez-Hernandez et al, 2017 ), cancers ( Luga et al, 2012 ; Jorfi et al, 2015 ; Kholia et al, 2015 ; Stratton et al, 2015a ; Sung et al, 2015 ; Tkach and Théry, 2016 ; Moore et al, 2017 ; Sung and Weaver, 2017 ) and neurodegenerative diseases ( Colombo et al, 2012 ; Gupta and Pulliam, 2014 ; Porro et al, 2015 ; Basso and Bonetto, 2016 ). In cancer patients, elevated EMV levels have for example been demonstrated in the blood ( Ginestra et al, 1998 ; Kim et al, 2003 ; Zwicker et al, 2009 ) and EMVs can also aid tumor spread and survival as they transport various micro RNAs, pathological growth factor receptors and soluble proteins ( Muralidharan-Chari et al, 2010 ; Inal et al, 2012 ; Hoshino et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer

et al. 2018

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Exosomes and microvesicles (EMV) are lipid bilayer-enclosed structures, released by cells and involved in intercellular communication through transfer of proteins and genetic material. EMV release is also associated with various pathologies, including cancer, where increased EMV release is amongst other associated with chemo-resistance and active transfer of pro-oncogenic factors. Recent studies show that EMV-inhibiting agents can sensitize cancer cells to chemotherapeutic agents and reduce cancer growth in vivo. Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, has anti-inflammatory and anti-oxidant properties, and displays anti-proliferative activity. Here we report a novel role for CBD as a potent inhibitor of EMV release from three cancer cell lines: prostate cancer (PC3), hepatocellular carcinoma (HEPG2) and breast adenocarcinoma (MDA-MB-231). CBD significantly reduced exosome release in all three cancer cell lines, and also significantly, albeit more variably, inhibited microvesicle release. The EMV modulating effects of CBD were found to be dose dependent (1 and 5 μM) and cancer cell type specific. Moreover, we provide evidence that this may be associated with changes in mitochondrial function, including modulation of STAT3 and prohibitin expression, and that CBD can be used to sensitize cancer cells to chemotherapy. We suggest that the known anti-cancer effects of CBD may partly be due to the regulatory effects on EMV biogenesis, and thus CBD poses as a novel and safe modulator of EMV-mediated pathological events.

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Extracellular Vesicles as Therapeutic Agents in Systemic Lupus Erythematosus

Cited by 50 publications

References 89 publications

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

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

Molecular interactions at the surface of extracellular vesicles

Cannabidiol (CBD) Is a Novel Inhibitor for Exosome and Microvesicle (EMV) Release in Cancer

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