What are exosomes?

What Are Exosomes?

Exosomes are small membrane-bound vesicles (30-200 nm in diameter) that are formed within multivesicular bodies (MVBs) in the endosomal system and released into the extracellular space when these MVBs fuse with the cell membrane. 1

Biogenesis and Formation

Exosomes originate through a distinct intracellular pathway that differentiates them from other extracellular vesicles:

• Exosomes are generated as intraluminal vesicles (ILVs) within multivesicular bodies through inward budding of the endosomal membrane 1
• The endosomal sorting complex (ESCRT) initiates cargo loading in early endosomes, continuing into late endosomes where ILVs accumulate 1
• When MVBs fuse with the plasma membrane, ILVs are released as exosomes into the extracellular space through exocytosis 1
• This biogenesis mechanism clearly distinguishes exosomes from microvesicles/microparticles, which bud directly from the plasma membrane during cellular activation or early apoptosis 1

Physical Characteristics and Markers

Exosomes possess specific physical properties and molecular markers:

• Size range: typically 30-200 nm in diameter, with most sources citing below 100 nm as the standard cutoff 1
• Cup-shaped morphology when visualized by electron microscopy 1
• Characteristic surface markers include heat shock protein HSP70 and tetraspanins CD63, CD9, and CD81 1
• Important caveat: Some markers like CD9 and CD81 may also be expressed on microvesicles, making precise identification challenging without demonstrating biogenesis pathway 1

Cargo and Composition

Exosomes carry diverse molecular cargo that reflects their cell of origin:

• Contain lipids, cytosolic proteins, messenger RNAs, microRNAs, and other non-coding RNAs 1
• Package DNA, proteins, lipids, metabolites, and even organelle fragments 1, 2
• The cargo composition is not random but reflects selective sorting mechanisms during MVB formation 1
• Critical distinction: Exosomal proteo-transcriptome may vary compared to their donor cell, which limits the extent to which exosomes perfectly mirror their parent cells 1

Functional Roles

Exosomes serve as intercellular communication vehicles with multiple physiological and pathological functions:

• Act as horizontal cell-to-cell communication routes, delivering cargo to recipient cells 1
• Originally considered cellular waste disposal systems, but now recognized as active signaling mediators 1
• Orchestrate physiological and pathological effects through their cargo and membrane composition 1
• Every human body cell type can release exosomes, including tumor cells 1

Clinical Significance

Exosomes have emerged as promising biomarkers and therapeutic tools:

• Present in all body fluids including blood, urine, and saliva, making them accessible for liquid biopsy applications 1, 3
• Show potential for early cancer screening and diagnosis, particularly before metastasis occurs 1
• Can be used for tumor monitoring as they represent a proxy for tissues from which they are released 1
• Dendritic cell-derived exosomes demonstrate immunotherapeutic potential as cell-free vaccines 4, 5

Nomenclature Context

Understanding current terminology is essential for interpreting the literature:

• The International Society for Extracellular Vesicles (ISEV) provides standardized nomenclature guidelines 1
• Exosomes are classified as small extracellular vesicles (sEVs) in current ISEV terminology 1
• The term "exosome" should only be used when the endosomal origin can be demonstrated; otherwise, "small EVs" is more appropriate 1
• Historical terms like "platelet dust" (described in 1967) and various other names have been consolidated under current standardized nomenclature 1

Key Distinguishing Features from Other Vesicles

Exosomes differ from other extracellular particles in critical ways:

• Size distinction: Exosomes (30-200 nm) are smaller than large EVs/microvesicles (100-1000 nm) and apoptotic bodies (>1000 nm) 1
• Biogenesis pathway: Endosomal origin versus direct plasma membrane budding distinguishes exosomes from ectosomes/microvesicles 1
• Density: Exosomes have a characteristic density of approximately 1.1-1.3 g/mL 1
• The size boundary between small and large EVs is not razor-sharp, with some sources citing 100 nm and others 150 nm as the cutoff 1