Extracellular Vesicles

Biological outsourcing

Extracellular vesicles (EVs) are membrane-bound entities that can’t replicate, but take diverse forms, perform many functions and reflect the physiological states of the cells from which they're derived—making them powerful tools for intercellular communication.

Renewed interest and classification

While EVs have been known about since the 1940s, their complex roles have emerged only gradually. When studies done in the mid-2000s revealed that these vesicles contain RNA, particularly microRNA (miRNA), interest peaked in their ability to mediate cell-to-cell information exchange within most cell and tissue types. More recently, intensive research has gone into adapting EV structure and function to develop drug-delivery systems and cell therapies of far greater efficacy than have existed until now.

To date, EVs have been isolated from most biological fluids including plasma, serum, urine, saliva, bronchial secretions, breast milk, amniotic fluid and seminal fluid. Some of the most-studied subtypes of extracellular vesicles include:

• Ectosomes: EVs that emerge via direct budding or "shedding" from of a cell's plasma membrane
• Exosomes: In contrast with ectosomes, these originate from intracellular budding and are later released by the cell
• Apoptotic bodies: EV remnants of cells that have undergone apoptosis, or programmed cell death
• Oncosomes: Larger (1–20 µm) EVs produced by cancer cells, neurons and other cell types that are nearly cells themselves, lacking only a full nuclear complement
• Microsomes: Small (20–200 nm) endoplasmic reticulum (ER)-derived EVs artificially produced during tissue homogenization and used for ER structure and function studies
• Liposomes: Phospholipid bilayer-delimited EVs able to separate inner and outer aqueous environments, now used extensively in biocompatible drug-delivery systems
• Micelles: Tiny (2–20 nm) lipid monolayer-delimited EVs enclosing a hydrophobic interior suitable for delivery of fat-soluble drugs and other compounds

Note that, by its broadest accepted definition, the term extracellular vesicle can also be applied to other common structures—both welcome and unwelcome in biological systems. These include platelets and red blood cells, which bud from their origin cells and/or lack the nuclei required for self-replication, and enveloped viruses, delimited by cellular membranes assembled from host-cell materials, but housing the protein products and nucleic acids of their own viral genome.

Once thought of as mere "garbage bags" for cellular waste products, EVs and their potential have become the focus of an already-fruitful global research effort that appears to be only in its early stages.