Exosomes, extracellular vesicles and the cellular secretome are related but scientifically distinct components of cell-to-cell communication. Understanding their differences is essential for laboratory manufacturing, product characterisation, clinical research and responsible medical communication.
These terms should not be used interchangeably. Each describes a different level or fraction of cellular secretion.
Extracellular vesicles, or EVs, are membrane-enclosed particles released by cells. They cannot replicate independently and may carry proteins, lipids, RNA, metabolites and other molecular components.
EV is the broad scientific category that includes heterogeneous vesicle populations produced through different cellular pathways.
Exosomes are a subtype of extracellular vesicle associated with formation inside endosomal multivesicular bodies and release following fusion with the plasma membrane.
Small particle size or expression of selected proteins does not independently prove endosomal origin.
The secretome is the complete biological output released by cells. It includes soluble proteins, cytokines, chemokines, growth factors, enzymes, metabolites, lipid mediators and extracellular vesicles.
The secretome is therefore broader than an EV or purified-exosome preparation.
When the intracellular origin of a vesicle population has not been demonstrated, the term extracellular vesicle or small extracellular vesicle is generally more scientifically accurate than exosome.
| Characteristic | Extracellular Vesicles | Exosomes | Secretome |
|---|---|---|---|
| Scientific scope | Broad category of cell-released membrane-enclosed particles. | EV subtype associated with endosomal biogenesis. | Complete soluble and vesicular output released by cells. |
| Principal form | Lipid-bilayer-enclosed particles. | Lipid-bilayer-enclosed particles formed through the endosomal pathway. | Complex mixture of soluble molecules and EVs. |
| Typical contents | Proteins, lipids, RNA, metabolites and other cell-derived cargo. | Similar molecular classes, with composition determined by source cells and biogenesis. | Cytokines, growth factors, enzymes, metabolites, lipids, proteins and EVs. |
| How obtained | Separated or enriched from conditioned medium or biological fluids. | Requires evidence supporting enrichment and endosomal origin. | Recovered through conditioned medium before or after downstream processing. |
| Primary development status | Research, biomarkers, drug delivery and investigational therapeutics. | Research and investigational therapeutic development. | Research and development of cell-free biologic fractions. |
Cells communicate through combinations of soluble molecules and membrane-enclosed vesicles. The resulting biological effect depends on the source cell, recipient cell, molecular cargo, concentration and tissue environment.
Cytokines, chemokines, growth factors, enzymes and metabolites may bind receptors or otherwise change recipient-cell behaviour.
EVs protect selected cargo within a lipid membrane and may interact with recipient cells through receptor binding, endocytosis or membrane interaction.
Secreted material may influence nearby cells without requiring the source cells to become permanently incorporated into the recipient tissue.
Secretome and EV components may influence macrophages, lymphocytes, dendritic cells and other immune-cell populations.
Cell-derived factors are studied for their effects on cellular survival, migration, angiogenesis, matrix biology and endogenous repair responses.
A preparation may produce different effects depending on source-cell health, culture conditions, recipient tissue, dose and route.
Exosomes, EVs and secretome are not differentiated. Source cells may be expanded, primed or lineage-directed; their released biological material is subsequently collected and processed.
Define cell identity, tissue origin, donor, passage number, viability and culture history.
Maintain cells under documented medium, supplement, oxygen, density and environmental conditions.
Source cells may be exposed to defined biochemical, inflammatory, hypoxic, mechanical or three-dimensional conditions to modify their secretory profile.
Cells release soluble and vesicular biological material into a defined collection medium.
Conditioned medium is collected under a controlled procedure designed to preserve traceability and quality.
Intact cells, debris and selected larger particles are removed through centrifugation, filtration or related processing.
The material may remain as complete conditioned medium or be divided into soluble, EV-enriched and EV-depleted fractions.
Ultrafiltration, chromatography, ultracentrifugation or combined methods may be used according to the intended product.
Evaluate composition, particle characteristics, contaminants, microbiological quality, stability and functional activity.
Exosomes, EVs and secretome fractions may be studied as biological products, analytical indicators or manufacturing intermediates.
Secretome and EV profiles may provide information about source-cell phenotype, stress, senescence or response to culture conditions.
Secreted biological material may be separated from living cells and developed as a defined cell-free product.
Changes in culture environment may be used to modify the composition or functional activity of secreted material.
Selected secreted factors or EV activities may support mechanism-related testing, although one universal potency assay does not apply to every product.
EVs may be loaded or engineered to carry selected RNA, proteins or pharmaceutical compounds.
EV and secretome profiles may help determine whether changes in media, scale, equipment or source cells alter the final product.
EVs and secretome fractions are routinely used to investigate communication between immune, stromal, vascular, neural and other cell populations.
EVs recovered from blood, urine, saliva, cerebrospinal fluid and other specimens are studied as potential indicators of disease or treatment response.
Natural and engineered EVs are being investigated as carriers for RNA, proteins and selected therapeutic compounds.
MSC-derived EV and secretome preparations are being studied as possible alternatives or complements to living-cell administration.
Early studies have examined selected secretome or EV preparations in wound, dermatological, ocular and local tissue-repair settings.
Broad therapeutic use for neurological, autoimmune, orthopaedic, cardiovascular or metabolic diseases has not been established as a universal standard of care.
These categories identify active research areas. They do not establish approval, safety or clinical effectiveness for a particular product.
Research includes cartilage, bone, tendon, muscle and inflammatory joint environments.
Studies examine epithelial repair, fibroblast behaviour, angiogenesis and extracellular-matrix signalling.
Research examines neuroinflammation, trophic support, vascular signalling and specialised delivery.
Secretome and EV components are studied for their interaction with innate and adaptive immune pathways.
Early development programmes examine inflammatory, vascular and epithelial responses in lung injury.
Research includes angiogenesis, myocardial injury, vascular function and cellular-survival pathways.
Studies examine inflammatory, vascular, anti-apoptotic and fibrosis-associated mechanisms.
Tumour- and immune-derived EVs are studied as biomarkers, therapeutic targets and drug-delivery platforms.
Engineered EVs are being developed to improve cargo loading, tissue targeting and controlled delivery.
Exosomes, EVs and secretome preparations are not inherently patient-specific. They may be developed through an individually assigned model or through controlled batch manufacturing.
A preparation may be linked to an individual patient when derived from autologous cells or manufactured under a named-patient protocol.
A product may be manufactured from a qualified allogeneic cell bank through a defined and repeatable process.
Source cells may be differentiated, primed or genetically modified, but the resulting EV or secretome preparation is collected, separated, purified, characterised and formulated.
A scalable process may support wider distribution, but scalability alone does not establish that the material is an authorised mass-market medical therapy.
Characterisation should integrate source-cell, particle, molecular, contaminant, microbiological, stability and functional information.
Document cell type, tissue origin, donor, passage, phenotype, viability and culture history.
Estimate particle concentration and size distribution while recognising that particle count does not establish EV identity.
Use electron microscopy or other appropriate imaging to assess membrane-enclosed structures.
Evaluate selected proteins, lipids, nucleic acids and soluble factors relevant to the preparation.
Assess soluble proteins, lipoproteins, aggregates, media components and process-related residuals.
Evaluate sterility-related parameters, mycoplasma and endotoxin where appropriate.
Use fit-for-purpose assays linked to the proposed mechanism rather than relying solely on particle number.
Compare critical attributes across source-cell batches, production runs and manufacturing changes.
Establish the effects of formulation, temperature, storage duration, transport and freeze–thaw exposure.
Exosomes, extracellular vesicles, small extracellular vesicles, secretome and conditioned medium describe related but distinct materials.
The word “exosome” should not be assigned solely on the basis of nanoscale size, selected surface proteins or one separation method.
Laboratory or animal activity does not independently establish clinical safety or effectiveness in human patients.
Preparations from different source cells, donors, laboratories and manufacturing processes cannot be presumed to be interchangeable.
In the United States, the FDA states that there are no FDA-approved exosome products. Regulatory status varies by jurisdiction, product composition, intended use and clinical claims.
These preparations should not be represented as established cures for neurological, autoimmune, orthopaedic, cardiovascular, metabolic or other diseases without product-specific clinical evidence and applicable authorisation.
Establish tissue origin, donor, cell identity, passage, phenotype and culture history.
Standardise culture medium, supplements, oxygen, cell density, priming and conditioning time.
Distinguish complete secretome, conditioned medium, EV-enriched material and EV-depleted fractions.
Integrate particle, molecular, contaminant, microbiological and stability information.
Use assays related to the proposed mechanism and intended biological application.
Separate established laboratory use, investigational medical development and authorised therapeutic use.
Journal of Extracellular Vesicles. 2024;13:e12404.
View publicationNature Reviews Molecular Cell Biology. 2018;19:213–228.
View publicationFrontiers in Immunology. 2018;9:2837.
View publicationTranslational and manufacturing considerations for MSC-derived EV products.
View publicationSystematic review of methods, efficacy and translational limitations.
View publicationScoping review of the EV clinical-development landscape.
View publicationRegulatory and patient-safety information concerning unapproved exosome products.
View FDA informationGuidance concerning quality and clinical-trial development of advanced biological products.
View EMA guidancePhysicians, researchers and institutions may request information concerning source-cell systems, secretome production, extracellular-vesicle separation, characterisation, functional assays and scientific collaboration.