Extracellular membrane vesicles as a mechanism of cell-to-cell communication: advantages and disadvantages

Abstract

Microvesicles represent a newly identified mechanism of intercellular communication. Two different types of microvesicles have been identified: membrane-derived vesicles (EVs) and exosomes. EVs originate by direct budding from the plasma membrane, while exosomes arise from ectocytosis of multivesicular bodies. Recent attention has focused on the capacity of EVs to alter the phenotype of neighboring cells to make them resemble EV-producing cells. Stem cells are an abundant source of EVs, and the interaction between stem cells and the microenvironment (i.e., stem cell niche) plays a critical role in determining stem cell phenotype. The stem cell niche hypothesis predicts that stem cell number is limited by the availability of niches releasing the necessary signals for self-renewal and survival, and the niche thus provides a mechanism for controlling and limiting stem cell numbers. EVs may play a fundamental role in this context by transferring genetic information between cells. EVs can transfer mRNA and microRNA to target cells, both of which may be involved in the change in target-cell phenotype towards that of EV-producing cells. The exchange of genetic information may be bidirectional, and EV-mediated transfer of genetic information after tissue damage may reprogram stem cells to acquire the phenotypic features of the injured tissue cells. In addition, stem cell-derived EVs may induce the de-differentiation of cells that survive injury by promoting their reentry into the cell cycle and subsequently increasing the possibility of tissue regeneration.

Cell‐to‐cell communication: microRNAs as hormones

“…Exosomes are the best characterized class of EVs; they are secreted by almost all cell types, are 40 to 100 nm in diameter, and are enriched in a 1.13–1.19 g·mL −1 fraction in a sucrose density gradient (Kanada et al ., 2015; Turturici et al ., 2014). The protein and lipid composition of exosomes reflects their cellular sources (Staubach et al ., 2009; Yim et al ., 2016).…”

Time-dependent release of extracellular vesicle subpopulations in tumor CABA I cells

“…It is well known that a variety of cells is able to secrete several types of EVs. When initially identified EVs were considered a form of waste elimination, whereas it has become clear that these membrane-enclosed structures are signaling packages able to interact with the extracellular matrix, by modifying it, and the surrounding cells, by stimulating or inhibiting these structures (2,3). EVs can transport several bioactive molecules, such as proteins, lipids and RNAs, and can propagate their content in recipient cells through horizontal transfer, thus having a significant impact on the surrounding extracellular matrix and cells (4).…”

“…In the same manner, MVs have been widely studied in several normal cell types, including platelets, fibroblasts, neuronal, epithelial, endothelial and red (10)(11)(12)(13), and even more widely analyzed in cancer cells (6,(14)(15)(16)(17)(18) for their role in tumor progression, evasion from apoptosis, drug resistance, immune-escape, and angiogenesis (2,3,19). The non-accidental production of EVs, in pathological and physiological events, is emphasized by the fact that they are not merely miniature parental cells, showing both similarities and differences compared to the molecular composition of the cells of origin (6,20).…”

Quantitative body fluid proteomics in medicine — A focus on minimal invasiveness

“…These circulating microvesicles found in many types of body fluid and in extracellular space play an important role in cell signaling and intercellular communication [193][194][195]. According to their biogenesis, the extracellular vesicles can be grouped as apoptotic blebs, exosomes and microparticles, but the nomenclature is not clear for the latter two [196].…”