exosomes

Exosomes are small extracellular vesicles released by many cell types into the extracellular space and body fluids. They range in diameter from about 30 to 150 nanometers and originate from the endosomal compartment. Exosome biogenesis begins when the inward budding of late endosomal membranes creates intraluminal vesicles within multivesicular bodies; when these MVBs fuse with the plasma membrane, the internal vesicles are released as exosomes.

Exosome contents include lipids, proteins such as tetraspanins CD9, CD63, CD81; components of the ESCRT machinery like Alix and TSG101; as well as nucleic acids including mRNA and miRNA. The cargo is often specific to the cell of origin and can be altered in disease. Exosome formation can proceed via ESCRT-dependent pathways or ESCRT-independent routes that rely on lipid microdomains and tetraspanins.

Function and uptake: Exosomes mediate intercellular communication by delivering cargo to recipient cells. They can be taken up by endocytosis, phagocytosis, macropinocytosis, or direct fusion, leading to modulation of gene expression and signaling pathways in target cells. They participate in immune regulation and antigen presentation, influence tissue repair and regeneration, and contribute to cancer progression and metastasis by preparing pre-metastatic niches and transferring oncogenic factors.

Clinical relevance and challenges: Because exosomes are present in blood, urine, cerebrospinal fluid, and other body fluids, they are investigated as noninvasive biomarkers for cancer and neurodegenerative diseases. They also hold interest as therapeutic delivery vehicles due to their stability and intrinsic targeting properties. Challenges include standardization of isolation and purification methods, heterogeneity of vesicle populations, defining specific markers, and achieving consistent, reproducible results across studies.