Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

Abstract

Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.

Diameters and Fluorescence Calibration for Extracellular Vesicle Analyses by Flow Cytometry

“…EVs are cell-derived vesicles detectable in many biological fluids and involved in the intercellular crosstalk, as well as in several physio-pathological processes, i.e., coagulation, inflammation, angiogenesis, tumor invasion, immune responses and proteolysis [ 7 , 10 , 11 , 12 , 13 , 44 , 45 ]. For these reasons, EVs have gained a prominent role as potential biomarkers in different clinical conditions [ 8 , 12 , 13 , 46 ]. Furthermore, EVs have been also proposed as a promising source of drug delivery vehicles [ 13 , 19 ].…”

“…For these reasons, EVs have gained a prominent role as potential biomarkers in different clinical conditions [ 8 , 12 , 13 , 46 ]. Furthermore, EVs have been also proposed as a promising source of drug delivery vehicles [ 13 , 19 ]. In particular, EVs released by mesenchymal stem cells (MSCs) have been demonstrated to have a critical regenerative and anti-inflammatory role, resulting effective in a number of preclinical and clinical studies for the treatment of many diseases and injuries [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

“…It has been demonstrated that EVs can be released by different pathogens [ 4 ] promoting their own dissemination [ 5 , 6 ]. In addition, mammalian EVs have been identified into many body fluids and have gained prominence as novel cell-to-cell communicators [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. EVs have been also proposed as potential biomarkers for prognosis and diagnosis of different clinical conditions [ 12 , 13 , 15 , 16 , 17 , 18 ].…”

“…The use of MSC-derived EVs, as an alternative to MSC themselves, produces many advantages, mainly related to their higher safety profiles. It has been observed that MSC-derived EVs have reduced levels of immunogenicity, they cross biological barriers, also avoiding complications linked to stem cell-induced ectopic tumor formation, entrapment in lung microvasculature, and immune rejection [ 13 , 20 ]. For these reasons, the rationale for developing EVs as an alternative therapeutic option results particularly strong.…”

Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

“…EVs carry proteins, nucleic acids, lipids and small molecules, whereby their specific cargo depends on the microenvironment and the pathophysiological state of the cell [ 6 ]. The transfer of EVs between cells may affect cell physiology but also play a role in the mechanisms of several diseases [ 7 , 8 ]. Besides their role in health and disease, EVs are considered as a rich source of biomarkers for the diagnosis of several diseases.…”