Abstract
Extracellular vesicles (EVs) — including exosomes, microvesicles and apoptotic bodies — have received much scientific attention last decade as mediators of a newly discovered cell-to-cell communication system, acting at short and long distances. EVs carry biologically active molecules, thus providing signals that influence a spectrum of functions in recipient cells during various physiological and pathological processes. Recent findings point to EVs as very attractive immunomodulatory therapeutic agents, vehicles for drug delivery and diagnostic and prognostic biomarkers in liquid biopsies. In addition, EVs interact with and regulate the synthesis of extracellular matrix (ECM) components, which is crucial for organ development and wound healing, as well as bone and cardiovascular calcification. EVs carrying matrix metalloproteinases (MMPs) are involved in ECM remodeling, thus modifying tumor microenvironment and contributing to premetastatic niche formation and angiogenesis. Here we review the role of EVs in control of cell function, with emphasis on their interaction with ECM and microenvironment in health and disease.
Highlights
Most cell types secrete different types of Extracellular vesicles (EVs) that can be found in all body fluids, as well as in cell culture supernatant
Many studies focus on endothelial progenitor cell (EPC)-based therapy, since these cells are involved in revascularization processes (Rafii and Lyden, 2003) and may drastically improve regeneration and patients’ outcome (Lara-Hernandez et al, 2010)
The response of endothelial cells to Delta-like 4 (Dll4)-containing exosomes seems to differ in a 2D cell culture from a chemically controlled 3D microenvironment with a vascular endothelial growth factor (VEGF) concentration gradient (Sharghi-Namini et al, 2014), suggesting that, in vitro, just as in vivo, tissue microenvironment represents an important factor in the exosome-mediated control of cell function
Summary
Most cell types secrete different types of EVs that can be found in all body fluids, as well as in cell culture supernatant. These molecules retain their biological function (Valadi et al, 2007) and may affect the function of recipient cells at a long distance, since they can travel in circulation encapsulated by the lipid bilayer This concept sheds new light on fundamental process of intercellular communication, beyond the need for direct cellto-cell contact or secretion of soluble factors that act only on neighboring cells. As a consequence of this mechanism, exosome transmembrane proteins retain the same orientation as that of the donor cell plasma membrane (Chaput et al, 2005), which allows their interaction with recipient cell receptors These surface proteins include tetraspanins (CD9, CD63, and CD81), integrins, ICAM1 (intercellular adhesion molecule 1) and phosphatidylserine, which is found on the surface of microvesicles and apoptotic bodies (Théry et al, 2009). We discuss the role of EVs in RNA and protein transfer between cells, influencing the invasion of tumor cells, immune evasion, dissemination of developmental signals during organogenesis and tissue repair, and calcification during bone development and pathological conditions, such arterial plaque and kidney stone formation
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