Extracellular vesicles (EVs) are important players for intercellular communication. EVs are secreted by almost all cell types; they can transfer information between nearby or distant cells, and they are highly abundant in body fluids. In this review, we describe the general characteristics of EVs, as well as isolation and characterization approaches. Then, we focus on one of the most relevant sources of EVs: the blood. Indeed, apart from EVs secreted by blood cells, EVs of diverse origins travel in the bloodstream. We present the numerous types of EVs that have been found in circulation. Besides, the implications of blood-derived EVs in both physiological and pathological processes are summarized, highlighting their potential as biomarkers for the diagnosis, treatment monitoring, and prognosis of several diseases, and also as indicators of physiological modifications. Finally, the applications of EVs introduced in the circulatory system are discussed. We describe the use of EVs from distinct origins, naturally produced or engineered, autologous, allogeneic, or even from different species and the effects they have when introduced in circulation. Therefore, the present work provides a comprehensive overview of the components, effects, and applications of EVs in blood.

The improvement of life quality and medical advances has resulted in increased life expectancy. Despite this, health status commonly worsens in the last years of life. Frailty is an intermediate and reversible state that often precedes dependency and therefore, its identification may be essential to prevent dependency. However, there is no consensus on the best tools to identify frailty. In this sense, diverse molecules have been proposed as potential biomarkers. Some investigations pointed to an increased chronic inflammation or inflammaging with frailty, while others did not report such differences. In this work, we evaluated the circulating concentration of the inflammaging markers in adults and older adults (aged over 70 years) by ELISA and Luminex techniques. The Barthel Index was applied for the evaluation of dependency and Timed up-and-go, Gait Speed, Short Physical Performance Battery, Tilburg Frailty Indicator and Gerontopole Frailty Screening Tool were used for the identification of frailty. CRP, TNF-α, IL-6 and albumin concentrations were measured, and we found that elevated inflammation is present in older adults, while no differences with frailty and dependency were reported. Our results were consistent for all the evaluated frailty scales, highlighting the need to reconsider increased inflammation as a biomarker of frailty.

Remyelination is a key aspect in multiple sclerosis pathology and a special effort is being made to promote it. However, there is still no available treatment to regenerate myelin and several strategies are being scrutinized. Myelination is naturally performed by oligodendrocytes and microRNAs have been postulated as a promising tool to induce oligodendrocyte precursor cell differentiation and therefore remyelination. Herein, DSPC liposomes and PLGA nanoparticles were studied for miR-219a-5p encapsulation, release and remyelination promotion. In parallel, they were compared with biologically engineered extracellular vesicles overexpressing miR-219a-5p. Interestingly, extracellular vesicles showed the highest oligodendrocyte precursor cell differentiation levels and were more effective than liposomes and polymeric nanoparticles crossing the blood–brain barrier. Finally, extracellular vesicles were able to improve EAE animal model clinical evolution. Our results indicate that the use of extracellular vesicles as miR-219a-5p delivery system can be a feasible and promising strategy to induce remyelination in multiple sclerosis patients.

Background Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Methods Leukocytes from 50 MS patients and 20 healthy controls (HC) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq and circRNA candidates were studied in a second cohort (70MS and 46HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Results Among the differentially expressed circRNAs, the 96.1% are upregulated in patients compared to controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined AUC of 0.852. Conclusion There is global, specific and sex dependent increase of circRNA expression in MS and 6 circRNAs are proposed as potential biomarkers.