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Review
. 2021 Jun 15;22(12):6417.
doi: 10.3390/ijms22126417.

Critical Review of the Evolution of Extracellular Vesicles' Knowledge: From 1946 to Today

Erica Bazzan  1 , Mariaenrica Tinè  1 , Alvise Casara  1 , Davide Biondini  1 , Umberto Semenzato  1 , Elisabetta Cocconcelli  1 , Elisabetta Balestro  1 , Marco Damin  1 , Claudia Maria Radu  2   3 , Graziella Turato  1 , Simonetta Baraldo  1 , Paolo Simioni  3 , Paolo Spagnolo  1 , Marina Saetta  1 , Manuel G Cosio  1   4
Affiliations
Review

Critical Review of the Evolution of Extracellular Vesicles' Knowledge: From 1946 to Today

Erica Bazzan et al. Int J Mol Sci. .

Abstract

Extracellular vesicles (EVs) are a family of particles/vesicles present in blood and body fluids, composed of phospholipid bilayers that carry a variety of molecules that can mediate cell communication, modulating crucial cell processes such as homeostasis, induction/dampening of inflammation, and promotion of repair. Their existence, initially suspected in 1946 and confirmed in 1967, spurred a sharp increase in the number of scientific publications. Paradoxically, the increasing interest for EV content and function progressively reduced the relevance for a precise nomenclature in classifying EVs, therefore leading to a confusing scientific production. The aim of this review was to analyze the evolution of the progress in the knowledge and definition of EVs over the years, with an overview of the methodologies used for the identification of the vesicles, their cell of origin, and the detection of their cargo. The MISEV 2018 guidelines for the proper recognition nomenclature and ways to study EVs are summarized. The review finishes with a "more questions than answers" chapter, in which some of the problems we still face to fully understand the EV function and potential as a diagnostic and therapeutic tool are analyzed.

Keywords: exosomes; liposomes; microvesicles; multivesicular bodies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Number of publications per year in PubMed from 1946 to 2021. After the first annual meeting of the International Society of Extracellular Vesicles (ISEV) in 2012, the number of original papers and reviews including any extracellular-vesicle-related terms (exosomes, microvesicles, microparticles, and extracellular vesicles) increased exponentially. EVs: extracellular vesicles; EM: electron microscopy; ISEV: International Society of Extracellular Vesicles; MISEV: Minimal Information for Studies of Extracellular Vesicles.
Figure 2
Figure 2
Cumulative number of publications. Comparative evolution of the use of different terms for EVs (exosomes, microvesicles or extracellular vesicles) in the literature from 1946 to 2021. EVs: extracellular vesicles; EM: electron microscopy; ISEV: International Society of Extracellular Vesicles; MISEV: minimal information for studies of extracellular vesicles.
Figure 3
Figure 3
Biogenesis and cargoes of exosomes. Exosome development begins with endocytosis to form early endosomes, later forming late endosomes by inward budding, and finally generating multivesicular bodies (MVBs). MVBs could then either undergo degradation (generating lysosomes) or merge with the cell membrane and, by exocytosis, release intraluminal endosomal vesicles that become exosomes into the extracellular environment. Reprinted with permission from Reference [51].
Figure 4
Figure 4
Proposed model of heterogeneous exosomal composition and subpopulations. Different subspecies exist within exosomes isolated from the same batch of cells. Exosomes can differ with regard to lipid, protein, and miRNA composition. “Potent” exosomal subspecies enriched with a high number of miRNA (depicted as purple and red vesicles) exist next to exosomes that are essentially devoid of nucleic acids. Reprinted with permission from Reference [54].
See this image and copyright information in PMC

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