Autoimmune demyelinating diseases—including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis—are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions. In this review, we discuss the potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles—and in particular exosomes—in the treatment of autoimmune demyelinating diseases, and provide an outlook for studies of their future applications.

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Background: Recently microRNAs (miRs) have been proposed as possible disease biomarkers in Multiple Sclerosis (MS) field. Among miRs, those secreted through microvesicles (MVs) may contribute to different disease phases. Methods: This is a case-control study performed at the Department of Medical and Surgical Sciences, University of Foggia, Italy. Patients have not been yet exposed to disease modifying therapies (DMTs) and had received a confirmed diagnosis of relapsing remitting MS (RRMS). We analyzed the serum level of 6 MVs miRs by using Quantitative Real-Time PCR, comparing RRMS to HCs, with a 2:1 ratio. Subsequently, the differentially expressed miRNAs, were further tested with receiving operator curves (ROC). We aimed to explore possible role of MVs miRs as disease biomarker at the time of diagnosis.Results: A total of 12 patients were enroled. MiR-181a and miR-125a had higher levels in RRMS patients when compared to HCs (p<.01 and p<.05 respectively). The ROC curve indicated that both miR-181a and 125a could be considered as biomarkers with an area under the curve of 0.896 (p=.014; 95% CI: 0.72–1.00) and 0.785 (p=.046; 95% CI:0.59–1.00) respectively.Conclusions: Our study suggested MVs miR-181a and 125a as possible disease biomarkers in early diagnosed RRMS patients, not yet exposed to DMTs.

Background: Recently microRNAs (miRs) have been proposed as possible disease biomarkers in Multiple Sclerosis (MS) field. Among miRs, those secreted through microvesicles (MVs) may contribute to different disease phases. Methods: This is a case-control study performed at the Department of Medical and Surgical Sciences, University of Foggia, Italy. Patients have not been yet exposed to disease modifying therapies (DMTs) and had received a confirmed diagnosis of relapsing remitting MS (RRMS). We analyzed the serum level of 6 MVs miRs by using Quantitative Real-Time PCR, comparing RRMS to HCs, with a 2:1 ratio. Subsequently, the differentially expressed miRNAs, were further tested with receiving operator curves (ROC). We aimed to explore possible role of MVs miRs as disease biomarker at the time of diagnosis.Results: A total of 12 patients were enroled. MiR-181a and miR-125a had higher levels in RRMS patients when compared to HCs (p<.01 and p<.05 respectively). The ROC curve indicated that both miR-181a and 125a could be considered as biomarkers with an area under the curve of 0.896 (p=.014; 95% CI: 0.72–1.00) and 0.785 (p=.046; 95% CI:0.59–1.00) respectively.Conclusions: Our study suggested MVs miR-181a and 125a as possible disease biomarkers in early diagnosed RRMS patients, not yet exposed to DMTs.