MSC Secretome
The complete mixture of soluble and vesicular factors released by mesenchymal stromal cells.
CELLMEX Scientific Library
Secretome Biology
The cellular secretome is the complete collection of soluble and vesicular factors released by cells into their surrounding environment. In mesenchymal stromal cell cultures, this includes proteins, cytokines, chemokines, growth factors, lipids, metabolites and extracellular vesicles.
Scientific Definition
The secretome is the complete cellular output
The term secretome refers to the complete collection of biological substances released by a cell population under defined conditions.
In MSC culture, the secretome includes freely soluble molecules and material carried within or associated with extracellular vesicles.
The secretome is not one uniform product. Its composition depends on the source cells, donor, passage number, culture medium, oxygen conditions, cell density, conditioning period, environmental signals and downstream processing.
Conditioned Medium
Culture medium collected after cells have released biological material into the surrounding environment.
EV-Enriched Fraction
A processed fraction enriched for extracellular vesicles relative to the original conditioned medium.
EV-Depleted Medium
Conditioned medium processed to reduce extracellular-vesicle content while retaining a proportion of soluble factors.
Biological Composition
Soluble and vesicular components act together
Secretome composition is complex and dynamic. No single growth factor, cytokine or extracellular-vesicle marker fully defines the biological activity of a secretome preparation.
Growth Factors
Secretome preparations may contain growth and survival-related signals, depending on the cell source and culture conditions.
- Angiogenic factors
- Tissue-support signals
- Cell-survival mediators
- Matrix-regulating factors
Cytokines and Chemokines
These proteins participate in immune communication, inflammation, cellular recruitment and tissue responses.
- Pro-inflammatory mediators
- Anti-inflammatory mediators
- Immune-regulatory signals
- Cellular recruitment signals
Extracellular Vesicles
Vesicular components may carry proteins, lipids, messenger RNA, microRNA and other biological material.
- Small extracellular vesicles
- Larger vesicle populations
- Vesicle-associated proteins
- Vesicular nucleic acids
Extracellular-Matrix Factors
Secreted proteins and enzymes may affect matrix structure, turnover and cell–matrix interactions.
Lipids and Metabolites
Lipid mediators and metabolites may contribute to signalling, membrane interactions and cellular metabolism.
Process-Related Components
Residual medium proteins, supplements, carrier proteins and other culture components may remain unless specifically reduced or removed.
Biological Activity
The secretome supports paracrine communication
Many effects attributed to MSCs are being investigated as consequences of signals released by the cells rather than permanent engraftment or direct replacement of damaged tissue.
Immunological Signalling
Secreted factors may influence innate and adaptive immune responses.
- T-cell activity
- Macrophage behaviour
- Dendritic-cell signalling
- Inflammatory mediator production
Tissue-Support Signalling
Secretome components are studied for their ability to influence cellular survival, proliferation, migration and repair-associated signalling.
Angiogenic Signalling
Selected soluble and vesicular factors may influence endothelial-cell behaviour and vascular development in experimental systems.
Matrix Remodelling
Proteins and enzymes within the secretome may affect extracellular-matrix production, degradation and tissue organisation.
Anti-Apoptotic Signalling
Experimental studies examine whether secreted factors support cell survival under inflammatory, metabolic or oxidative stress.
Intercellular Communication
Soluble molecules and extracellular vesicles may transfer biological signals between the originating MSCs and recipient cells.
Laboratory Production
From MSC culture to a secretome preparation
Production requires control of both the originating cells and the environment in which secreted factors are generated.
Source-Cell Qualification
Define the MSC tissue source, donor information, identity, passage number and culture history.
Cellular Expansion
Expand the MSC population under controlled culture conditions before secretome collection.
Conditioning Phase
Maintain the cells in a defined medium for a specified period during which soluble and vesicular factors accumulate.
Medium Collection
Collect the conditioned medium using a documented procedure designed to control contamination and cell debris.
Clarification
Remove cells, large debris and selected particulate material through centrifugation, filtration or related processes.
Fractionation or Concentration
Concentrate the complete preparation or separate soluble and extracellular-vesicle fractions according to the project objective.
Formulation and Storage
Prepare the selected final presentation and define storage, freeze–thaw and handling conditions.
Quality Review
Review composition, microbiological safety, process documentation and relevant functional or potency-related data.
Manufacturing Variables
Culture conditions define the biological output
Two preparations described as MSC secretome cannot be assumed to have equivalent composition or biological activity.
Tissue Source
Bone-marrow, adipose and perinatal-tissue MSCs may produce different secretory profiles.
Donor and Cell Condition
Donor characteristics, cellular age, passage and senescence may affect secretome composition.
Culture Medium
Basal medium, supplements, serum exposure and chemically defined components may affect the final preparation.
Oxygen and Environment
Oxygen tension, temperature, confluence and cellular stress may alter secretory activity.
Priming or Preconditioning
Exposure to selected inflammatory, hypoxic or other signals may intentionally change the biological profile.
Processing and Storage
Filtration, concentration, fractionation, freezing, thawing and storage duration may affect stability and activity.
Characterisation and Quality Control
Secretome quality requires more than total protein measurement
Analytical testing should reflect the composition, manufacturing process and intended biological function of the preparation.
Source-Cell Identity
Document MSC source, culture history, immunophenotype and relevant cellular-quality information.
Total Protein and Composition
Measure overall protein content and, where appropriate, selected cytokines, growth factors or other components.
Extracellular-Vesicle Assessment
Evaluate particle concentration, size, morphology, markers and possible non-vesicular contaminants where an EV fraction is claimed.
Microbiological Safety
Assess sterility-related parameters, mycoplasma and endotoxin where relevant to the intended use.
Functional Testing
Use fit-for-purpose assays linked to the proposed biological mechanism or potency-related activity.
Stability
Evaluate storage duration, temperature, freeze–thaw exposure, container compatibility and changes in biological activity.
Translational Research
Principal areas of secretome investigation
Most proposed applications remain areas of laboratory, preclinical or early clinical investigation and should be described according to their actual evidence level.
Wound and Skin Biology
Investigation of fibroblast activity, matrix remodelling, angiogenic signalling and epithelial repair.
Musculoskeletal Research
Study of secretome effects on cartilage, tendon, bone and inflammatory joint environments.
Immune Modulation
Evaluation of soluble and vesicular signals that influence inflammatory and immune-cell behaviour.
Neurological Research
Investigation of neuroprotective, neuroinflammatory and trophic signalling in experimental systems.
Pulmonary and Organ Injury
Preclinical research examining inflammatory, vascular and tissue-support mechanisms in organ injury models.
Manufacturing Science
Development of reproducible production, concentration, fractionation, formulation and potency-assessment methods.
Clinical and scientific qualification
The terms secretome, conditioned medium, purified exosomes and extracellular-vesicle preparation should not be used interchangeably. They describe different materials and processing states.
Biological activity demonstrated in laboratory or animal models does not by itself establish safety or effectiveness in patients.
Secretome preparations produced by different laboratories cannot be assumed to be equivalent. Source cells, culture conditions, collection, fractionation, concentration, formulation and storage may materially alter the final product.
Secretome and conditioned-media products should not be represented as established cures for neurological, autoimmune, metabolic, orthopaedic, dermatological or other diseases without appropriate product-specific clinical evidence.
The CELLMEX Approach
A complete secretome programme requires defined fractions
Defined Source Cells
Tissue origin, cellular identity, passage number and culture history should be documented.
Controlled Conditioning
Medium composition, cell density, conditioning period and environmental conditions should be defined.
Fraction-Specific Processing
Complete secretome, EV-enriched and EV-depleted preparations should be processed and described separately.
Functional Characterisation
Composition, microbiological quality, stability and biological activity should be interpreted together.
Selected Scientific References
MSC secretome biology and translational development
Ferreira JR, et al. Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning.
Frontiers in Immunology. 2018;9:2837.
View publicationKumar P, et al. The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine.
Cytokine & Growth Factor Reviews. 2019;46:1–9.
View publicationCunningham CJ, et al. The therapeutic potential of the mesenchymal stem cell secretome in ischaemic heart disease.
Swiss Medical Weekly. 2018;148:w14650.
View publicationSkalnikova HK. Proteomic techniques for characterisation of mesenchymal stem cell secretome.
Biochimie. 2013;95(12):2196–2211.
View publication
Scientific Information
Explore CELLMEX secretome research and laboratory capabilities
Physicians, researchers and institutions may request information concerning conditioned media, secretome fractionation, extracellular-vesicle processing, characterisation and research collaboration.