With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

Multiple sclerosis (MS) is a central nervous system (CNS) degenerative disorder which is caused by a targeted autoimmune-mediated attack on myelin proteins.Previously, mesenchymal stem cells were considered as a novel and successful treatment of MS. One of the underlying mechanisms behind their immunomodulatory function is the release of extracellular vesicles, particularly exosomes. In this study, we aimed to evaluate the suppressive efficacy of MSCs and their exosomes on the proliferation of peripheral mononuclear blood cells (PBMC) in relapsing-remitting MS (RRMS) patients and healthy subjects. To do, mesenchymal stem cells were derived from human umbilical cord tissues and used for exosome isolation through ultracentrifugation. Suppressive function of MSCs and MSC-derived exosomes was examined in a coculture with CFSE-labelled PBMCs in vitro. PBMC proliferation of the patients and healthy individuals was measured using flow cytometry. We first demonstrated that proliferation of PBMCs decreased in the presence of MSCs and suppression was more efficient by MSC-derived exosomes, with a minimum alloreaction rate. However, suppression capacity of MSCs and their exosomes significantly decreased during extensive sub-culturing. The present study showed that MSC-derived exosomes as an effective cell-free therapy could prevent proliferation of PBMCs. However, further evaluations are need to move towards a functional approach that can be translated to the clinic.

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Purpose: Multiple sclerosis (MS) is a debilitating neuroinflammatory disorder of the central nervous system. It is believed to result from an impaired immune response against myelin components especially myelin oligodendrocyte glycoprotein (MOG). Some efforts have been made to bioconjugate the MOG peptides to tolerogenic particles like poly (lactic-co-glycolic acid) (PLGA) for treating animal models of autoimmune disorders. Accordingly, we aimed to elucidate the tolerogenic effects of MOG-PLGA particles on experimental autoimmune encephalomyelitis (EAE). Methods: PGLA nanoparticles were synthesized using water/oil/water procedure. Next, the MOG or ovalbumin (OVA) peptides covalently linked to the PLGA particles. These particles were then intravenously or subcutaneously administered to nine groups of C57BL/6 mice before and after EAE induction. The brain tissues were assessed for the infiltration of immune cells. The Tolerogenic effect of the vaccine was also assessed on the quantity of the Treg cells. Moreover, the amount of interferon-γ (IFN-γ), interleukin-10 (IL-10), and interleukin-17 levels produced by splenic lymphocytes were then quantified by ELISA. Results: Intravenous administration of PLGA500-MOG35-55 nanoparticles before EAE induction ameliorated EAE clinical scores as well as infiltration of immune cells into the brain. In the spleen, the treatment increased CD4+CD25+FoxP3+ Treg population and restored the homeostasis of IFN-γ, IL-10, and IL-17 (all p values <0.0001) among splenocytes. Conclusion: The conjugation of MOG peptides to the PLGA nanoparticles significantly recovered clinical symptoms and the autoimmune response of EAE. The MOG-PGLA particles are potentially valuable for further evaluations, hopefully progressing toward an optimal approach that can be translated to the clinic.

Background. It is uncertain if omega-3 polyunsaturated fatty acids are associated with increase in resting metabolic rate (RMR) in adults. Objective. The aim of the present study was to evaluate the overall effects of omega-3 on RMR. Methods. Both PubMed and Scopus libraries were searched up to April 2021. Study quality was assessed using the Jadad scale. Random- and fixed-effects models were utilized in order to obtain pooled estimates of omega-3 supplementation impacts on RMR, using weight mean difference (WMD). Results. Seven studies including a total of 245 participants were included. There was significantly higher FFM-adjusted RMR in the intervention group than the control group (WMD: 26.666 kcal/kg/day, 95% CI: 9.010 to 44.322, p = 0.003 ). Study quality showed that four of seven included studies were of high quality. However, there was no significant difference in results in the subgroup analysis according to the quality of studies. Subgroup analyses revealed significant changes for sex (for women: WMD = 151.793 kcal/day, 95% CI = 62.249 to 241.337, p = 0.001 ) and BMI (for BMI > 25: WMD = 82.208 kcal/day, 95% CI = 0.937 to 163.480, p = 0.047 ). Influence analysis indicated no outlier among inclusions. Conclusion. The current study depicted that omega-3 polyunsaturated acids can significantly increase RMR in adults. However, further assessments of omega-3 supplementation therapy are critical to monitor its long-term outcomes and potential clinical application.

Purpose: Promising advances have been made in mesenchymal stem cell transplantation to re-induce the immune tolerance in neuroinflammatory animal models and Multiple Sclerosis patients. The available evidence demonstrated that immunomodulatory effects of mesenchymal stem cell are particularly exerted through releasing exosomes to their environment. We therefore, aimed to comparatively assess the potential effect of mesenchymal stem cells and mesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25− conventional T cells, isolated from relapsing-remitting Multiple Sclerosis patients. Methods: Mesenchymal stem cells were isolated from human umbilical cord tissues and used for exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymal stem cells-derived exosomes were evaluated for their anti-inflammatory effects against the proliferation of T cells isolated from two groups of individuals in vitro, MS patients and healthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, and interleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals. Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferation and percentage of conventional T cells that produce IFN-γ (healthy control: p<0.001) and interleukin-17 (healthy control: p<0.001, MS patients: p<0.001), with a significant increase of IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derived exosomes demonstrated higher immune-modulating properties on conventional T cells responses, compared to MSCs. Conclusion: The current study, provides a novel approach of exocytosis on autoimmune therapy. In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics, could be considered as an alternative for Mesenchymal stem cells in treating multiple sclerosis.