Abstract
All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ‘garbage bags’ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs) to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood–brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we’ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.
Highlights
Transfer of genetic information between cells had been proposed through only two mechanisms: vertical gene transfer,from parent to the generation,and horizontal gene transfer, induced through bacteriophages [1] or viruses [2]
Exosomes are the only vesicles of endocytic origin from inward budding of cell membranes [i.e. multivesicular endosomes (MVEs) [9]]; these vesicles directly fuse with the inner surface of the plasma membrane and release exosomes into the extracellular space [10], whereas microvesicles are shed by direct budding from the plasma membrane to the extracellular space
Confusions exist in the literature on the origin and nomenclature of Extracellular vesicles (EVs) because vesicles with the size of exosomes that bud at the plasma membrane have been called exosomes [11]
Summary
Transfer of genetic information between cells had been proposed through only two mechanisms: vertical gene transfer,from parent to the generation,and horizontal gene transfer, induced through bacteriophages [1] or viruses [2]. Extracellular vesicles (EVs) are produced constitutively by most, if not all, cell types and, interestingly, contain both, mRNAs and noncoding RNAs such as small regulatory microRNAs (miRNAs) as well as proteins that can be functionally delivered between different cell types and across species [3]. As a result, such vesicles have a significant impact on physiological processes. The peripheral blood of healthy individuals has been observed to contain ∼1010/ml of blood [7,8]
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