September 27th, 2024

A Brief Overview of Extracellular Vesicles

Extracellular vesicles (EVs) are reasonably well-defined within the EV-enthusiast community. Extracellular Vesicles (EVs) are spheroid and ellipsoid lipid bilayers that contain carbohydrates, RNA, DNA, and proteins within the EV and on its surface. EVs always contain transmembrane proteins and cholesterol. In relatively rare instances, EVs can contain vesicles. EVs are abundant in every biofluid. For instance, there are roughly 10 billion EVs per mL of plasma. Cells from all life domains produce EVs that often contain very distinct biomarkers distinct from each other. The difference in biomarker abundance tends to maintain some difference within the same cell type, for EVs originating from the same cell type are very heterogeneous.

The Biogenesis of Extracellular Vesicles

Extracellular vesicles are classically categorized into three groups by their mechanism of origination. These three categories are exosomes, microvesicles (sometimes called ectosomes), and apoptotic bodies. The generation of exosomes starts off with the invagination of the cell's membrane (also called endocytosis) to create an endosome within the cytoplasm (inner fluid of the cell). This endosome contains extracellular fluid. Once the endosome invaginates cell cargo and cytosol within smaller spherical lipid bilayers on its interior, the endosome is now categorized as a multivesicular body (MVB), and its internal spherical cargo holders are categorized as intraluminal vesicles. The MVB is then transported to and fuses with the cell's membrane to release these vesicles—now categorized as exosomes—into the lumen. These exosomes typically range in size from 30nm to 150nm. Microvesicles generally have a simpler biogenesis compared to exosomes. Microvesicles are formed by the outward budding and pinching of a cell's plasma membrane.

Apoptosis's vesicle formation process is more complicated than the exosome biogenesis pathway. Firstly, it is crucial to understand that apoptosis is the process of programmed cell death. Generally, apoptosis occurs through three pathways: the intrinsic, extrinsic, and Perforin/Granzyme pathways. All of these pathways converge to the activation of caspase-3. This activation and process ultimately cause endonuclease activation to degradation of chromosomal DNA, protease activation to degrade nuclear and cytoskeletal proteins, nuclear fragmentation, and the formation of apoptotic bodies through blebbing. The resultant apoptotic bodies (which range in size from 100nm to 1000nm) are typically engulfed by our immune cells (specifically macrophages), parenchymal cells, or neoplastic cells. Once the apoptosomes are engulfed, they are typically broken down by lysosomes.

Roles of Extracellular Vesicles in the Human Body

It is essential to understand that the high energy investment—that cells place into the process-intensive formation of extracellular vesicles—in most instances serves a beneficial role for the living organism. One of the three methods for intercell communication is the exchange of extracellular vesicles. This intercell communication often helps the organism to maintain homeostasis. (Homeostasis is adjusting biological systems to bring an organism's body to an optimal internal state). Exosomes are used for interneuron communication, which is crucial for organism movement and cognition. EVs can be beneficial from human to human. For instance, the EVs in breast milk have been shown to increase the speed of epithelial gap closures (which helps develop a baby's gastrointestinal tract) and regulate the infant's immune response.

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