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Table 1. Nomenclature and basic characteristics of several subtypes of EVs
Subpopulations of EVs
Characteristics of EVs Microvesicles (ectosomes, Ref.
Exosomes (small EVs) Apoptotic bodies
medium/large EVs)
Diameter, nm 40-100 100-1000 50-2000 [17]
Origin Endocytic membrane Cell membrane Apoptotic cells [18]
2+
Mechanism of delivery Ceramide-dependent, Ca depending phospholipid thin membrane protrusion and [20,21]
tetraspanin-dependent, and redistribution and Rho-kinase- blebbing of the apoptotic cells’
ESCRT-dependent exocytosis mediated myosin light chain surface
of multi vesicular bodies phosphorylation, facilitating
budding and blebbing
Phosphatidylserine Low High High [22]
composition
Complexity/granularity High High Low [26,27]
Components Cytoplasmic and membrane Adhesive molecules (ICAMs, Mitochondria, MHC [28,29,31,35]
molecules, proteins and lipids, PECAM-1, MCAM), membrane II molecules, ICAM-3,
tetraspanin’s receptors regulatory proteins (Rab), phosphatidylserine, sialylated
lipids (SpL, PL, LPS, LPS) and glycosylated ligands
and receptors (tetraspanin’s
receptors, LAIR-1, EGFR),
enzymes (Rab GTPase, ERK,
MLCK, TPI-1, HMGCL),
immune system proteins
(CD14, CD276, MiC-
11), apoAII, SOD, β-actin,
α-actin-4, HSP90AB1,
cytochrome complex, SCP-2
Nuclear fractions mRNA and microRNA, other non-coding RNAs non-coding RNAs
non-coding RNAs
Specific surface markers Tetraspanins (CD9, CD63, CD CD40, Phosphatidylserine, Annexin A5,
81), ESCRT machinery proteins integrins, selectins, ESCRT phosphatidylserine, caspase 3,
(Alix, tumor susceptibility gene machinery proteins (Alix, histones
10), flotillin-1 Vps4)
Key functional role Cell-to-cell communication, Cell-to-cell communication, Cell-to-cell communication,
cargo cargo cell clearance

SOD: superoxide dismutase; HSP: heat shock protein; SCP-2: sterol carrier protein 2; TPI-1: triosephosphate isomerase 1; HMGCL:
3-hydroxy-3-methylglutaryl-CoA lyase; ESCRT: endosomal sorting complexes required for transport; ERK: a prototypic mitogen-activated
protein kinase; EVs: extracellular vesicles

BASIC CHARACTERISTICS OF EV SUBSETS
Small EVs
Small EVs are also known as exosomes. They are a derivate of the endocytic membrane with an average
diameter of 40-100 nm and are released from several types of cells as a result of exocitosis and production
of multi vesicular bodies [18,19] . Multi vesicular bodies move along intracellular tubules, fuse with the plasma
membrane and release exosomes into the extracellular space. Small EVs have various cellular components
including cytoplasmic and membrane molecules, proteins, hormones (aldosterone), growth factors
(vascular endothelial growth factor, transforming growth factor), cytokines [interleukin (IL)-1β, IL-6, IL-8]
and lipids, as well as fragments of chromatin, such as non-coding RNAs and several inactive forms of
micro RNAs [18,19] . There is also a common set of membrane and cytosolic proteins, which are embedded
[20]
into exosomes that have originated from distinct cell types . The specific surface markers that ensure
recognition of the exosomes are tetraspanins (CD9, CD63, CD81), ESCRT (endosomal sorting complexes
[21]
required for transport) machinery proteins (Alix, tumor susceptibility gene 10), and flotillin-1 .

Medium/large EVs
Medium/large EVs (also known as microvesicles, micro particles, ectosomes) range in diameter from 100
[22]
to 1000 nm and result from budding of the cell membrane . Medium/large EVs are heavily enriched in
phospholipids, such as phosphatidylserine and phosphatidylcholine, and numerous membrane-dependent
[23]
structures (receptors, CD markers) that originated from the parent cells . Proteomics and lipidomics