Extracellular vesicles (EVs) are tiny, membrane-bound particles released by almost all cell types into the surrounding environment. These microscopic sacs act as cellular messengers, allowing cells to communicate. They are naturally occurring structures, distinct from cells and lack the ability to replicate independently. EVs are found in various bodily fluids, including blood, urine, and saliva, facilitating communication both locally and over longer distances within the body.
Formation and Release from Cells
Cells produce and release extracellular vesicles through distinct pathways. One method involves the direct outward budding of the cell’s outer membrane, pinching off small vesicles known as microvesicles or ectosomes. These microvesicles typically range in size from 100 to 1000 nanometers in diameter.
Another pathway involves the endosomal system, leading to the formation of exosomes. This process begins with inward budding of the cell’s plasma membrane, forming early endosomes that mature into multivesicular bodies (MVBs). Within these MVBs, the internal membrane further buds inward, creating smaller vesicles called intraluminal vesicles (ILVs) inside the larger MVB. When the MVB eventually fuses with the cell’s outer membrane, these enclosed intraluminal vesicles are released into the extracellular space as exosomes. Exosomes are generally smaller than microvesicles, typically measuring between 30 and 150 nanometers in diameter.
Composition and Cargo
Extracellular vesicles possess an outer shell composed of a lipid bilayer, similar to the parent cell’s membrane. This membrane encloses and protects the specific contents carried by the vesicle. The molecules packaged inside an EV are referred to as its cargo, which is a curated collection of information from the parent cell.
The cargo carried by EVs is diverse and includes various types of biomolecules. Proteins are a significant component, including structural proteins, enzymes, and signaling molecules. Lipids, such as cholesterol and ceramides, are also present, contributing to the vesicle’s membrane structure and sometimes acting as signaling molecules. Furthermore, EVs carry nucleic acids, including messenger RNA (mRNA) and various non-coding RNAs like microRNA (miRNA) and long non-coding RNA (lncRNA). These nucleic acids can influence gene expression in recipient cells.
Biological Roles in the Body
Extracellular vesicles facilitate information exchange between cells throughout the body. They enable biological processes by delivering their cargo to target cells, altering their behavior. This communication can occur between adjacent cells or between distant cells via circulation in bodily fluids.
EVs regulate the immune system. Immune cells release EVs containing specific proteins and nucleic acids that can either activate or suppress immune responses, influencing inflammation and pathogen defense. They also contribute to tissue repair and regeneration by delivering growth factors and signaling molecules that promote cell proliferation and differentiation in damaged areas. EVs are involved in removing cellular waste. When a recipient cell takes in an EV, either by fusion with its membrane or by endocytosis, its cargo is released, leading to changes in its protein synthesis, metabolic activity, or overall function.
Medical and Scientific Significance
Extracellular vesicles have garnered scientific interest for their potential applications in medicine. EVs can serve as biomarkers for various diseases. Since EVs are released by cells and circulate in body fluids, their specific cargo can reflect the physiological state of their originating cells. For instance, EVs released by cancer cells often carry distinct proteins or nucleic acids that differ from those released by healthy cells. Analyzing these specific EV markers in a simple blood sample can potentially detect diseases like cancer early, offering a less invasive alternative to traditional tissue biopsies, often called “liquid biopsies.”
Beyond diagnostics, EVs are explored for their therapeutic potential as drug delivery systems. Scientists are engineering EVs to encapsulate therapeutic agents like drugs, genetic material, or proteins. Because EVs are naturally recognized and taken up by cells, they can deliver these therapeutic payloads directly to diseased tissues or cells with high specificity. This targeted delivery could enhance treatment effectiveness while minimizing systemic side effects on healthy cells, aiding in treating conditions from cancer to neurodegenerative disorders.