Stromal Cell Population
A cultured population of adherent cells associated with the structural and signalling environment of tissues.
CELLMEX Scientific Library
MSC Biology
Mesenchymal stromal cells are culture-expanded, plastic-adherent cellular populations studied for their differentiation capacity, secretory activity, immunomodulatory effects and potential role in tissue repair and regenerative medicine.
Scientific Definition
Mesenchymal stromal cells within regenerative medicine
The abbreviation MSC is commonly used for mesenchymal stromal cells and, in some contexts, mesenchymal stem cells.
The term mesenchymal stromal cell is generally more scientifically appropriate for heterogeneous, plastic-adherent cell populations expanded from tissues such as bone marrow, adipose tissue and perinatal tissues.
A true stem cell must demonstrate both self-renewal and the ability to generate defined differentiated progeny. Routine surface-marker analysis and laboratory differentiation alone do not prove that every cell within an MSC culture is an individually multipotent stem cell.
Multipotent Potential
Under defined laboratory conditions, MSC populations can demonstrate differentiation toward selected mesenchymal lineages.
Secretory Activity
MSCs release soluble factors, extracellular vesicles and other signals capable of influencing nearby cells and tissues.
Tissue Sources
MSC populations can be isolated from several tissues
Cells obtained from different tissues should not be assumed to have identical growth, secretory, immunological or differentiation properties.
Bone Marrow
The historically best-characterised source of culture-expanded MSCs and an important reference source for defining MSC identity.
Adipose Tissue
A comparatively accessible source containing stromal progenitor populations that can be isolated and expanded under defined conditions.
Umbilical Cord Tissue
Perinatal tissue, including Wharton’s jelly, may provide stromal populations with distinct proliferative and secretory characteristics.
Placental Tissues
Several placental compartments may contain stromal-cell populations, although isolation and characterisation methods vary.
Dental and Other Tissues
Stromal populations have also been studied from dental pulp, synovium and other connective tissues.
Autologous and Allogeneic Sources
Cells may originate from the patient or a separate donor. Each approach carries different manufacturing, clinical and regulatory considerations.
Identification and Characterisation
Minimum laboratory criteria for culture-expanded MSCs
The International Society for Cellular Therapy established three widely used minimum criteria for describing human culture-expanded MSC populations.
Plastic Adherence
The cells should demonstrate adherence to tissue-culture plastic when maintained under standard culture conditions.
Immunophenotype
The population should demonstrate the expected pattern of positive and negative surface markers.
- Positive: CD105, CD73 and CD90
- Negative or low: CD45 and CD34
- Negative or low: CD14 or CD11b
- Negative or low: CD79α or CD19
- Negative or low: HLA-DR
In-Vitro Differentiation
Under defined laboratory conditions, the cells should demonstrate differentiation toward osteogenic, adipogenic and chondrogenic lineages.
Minimum criteria are not complete release criteria
Meeting basic MSC identity criteria does not establish sterility, genomic stability, clinical potency, manufacturing consistency or suitability for a particular treatment.
A clinical-grade preparation requires additional product-specific quality, safety and functional assessment.
Biological Activity
MSC activity extends beyond direct differentiation
Current research indicates that many MSC effects are associated with secreted factors, cell-to-cell interactions and modulation of the local biological environment.
Paracrine Signalling
MSCs release a complex mixture of soluble factors and extracellular vesicles that may influence nearby cells.
- Cytokines
- Chemokines
- Growth factors
- Extracellular vesicles
- Matrix-modulating factors
Immunomodulation
MSC populations have been studied for their ability to interact with innate and adaptive immune pathways.
- T-cell responses
- B-cell activity
- Macrophage behaviour
- Dendritic-cell function
- Natural-killer-cell responses
Tissue-Support Signalling
MSC-derived signals are investigated for their potential effects on vascularisation, cellular survival, extracellular-matrix remodelling and local repair responses.
Injury-Responsive Behaviour
The functional response of MSCs may be influenced by inflammatory signals, oxygen conditions, cellular stress and the surrounding tissue environment.
Differentiation Potential
MSCs can demonstrate lineage-associated differentiation in vitro, although this does not mean that administered cells routinely replace damaged tissues in patients.
Extracellular-Vesicle Release
MSCs release extracellular vesicles containing proteins, lipids and nucleic acids that may contribute to intercellular signalling.
Laboratory Expansion
From source tissue to a final cell preparation
Manufacturing conditions can materially influence MSC identity, viability, function and consistency.
Source-Material Qualification
Document the donor or tissue source, collection process, transport conditions, eligibility and traceability.
Cell Isolation
Recover the target stromal population using a method appropriate to the selected tissue.
Primary Culture
Establish adherent cultures under defined media, supplement, temperature and atmospheric conditions.
Cellular Expansion
Expand the cells while controlling passage number, confluence, culture duration and population growth.
Harvest and Processing
Recover, wash, count and prepare the cells while limiting unnecessary manipulation and loss of viability.
Cryopreservation
Where applicable, preserve cells using a controlled freezing process and qualified storage conditions.
Recovery and Formulation
Thaw or recover the preparation, evaluate post-thaw quality and formulate the required final presentation.
Quality Review
Review identity, viability, microbiological safety, documentation and acceptance criteria before release or research use.
Quality Control
MSC quality cannot be determined by cell count alone
Clinical or research preparations require a multidimensional assessment of identity, safety, consistency and biological function.
Identity
Morphology, adherence, immunophenotype and other product-specific identity characteristics.
Cell Number and Viability
Total cell count, viable-cell concentration and post-processing or post-thaw recovery.
Microbiological Safety
Sterility-related testing, mycoplasma assessment and endotoxin control where applicable.
Purity
Assessment of unwanted cell populations, residual process materials and other potential impurities.
Functional Assessment
Fit-for-purpose assays designed to measure a relevant biological or potency-related activity.
Stability and Consistency
Evaluation of passage-related changes, cryopreservation effects, batch variability and storage limitations.
Translational Research
Principal areas of MSC investigation
MSC research extends across cellular biology, immunology, tissue engineering, cell-free products and clinical translation.
Musculoskeletal Research
Investigation of cartilage, bone, tendon, ligament and joint-related tissue-support mechanisms.
Immune-Mediated Disorders
Study of MSC interactions with inflammatory and immune pathways in carefully defined disease settings.
Neurological Research
Investigation of neuroinflammatory, trophic and cell-signalling mechanisms rather than presumed direct neuronal replacement.
Wound and Vascular Biology
Study of paracrine signalling associated with angiogenesis, tissue survival and wound repair.
Secretome and Extracellular Vesicles
Evaluation of the soluble and vesicular factors released by MSC cultures.
Tissue-Directed MSCs
Research into controlled culture conditions that influence lineage-associated characteristics and biological function.
Clinical and scientific qualification
MSCs obtained from different tissues, donors or manufacturing processes cannot be assumed to be equivalent.
Laboratory differentiation, secretory activity or effects observed in experimental models do not by themselves establish clinical safety or effectiveness in patients.
Many proposed MSC applications remain investigational. Clinical use should be evaluated according to the specific product, indication, evidence, manufacturing standards, patient risk and applicable regulatory requirements.
MSC-based interventions should not be represented as established cures for progressive neurological, autoimmune, metabolic, cardiovascular or musculoskeletal diseases without appropriate product-specific clinical evidence.
The CELLMEX Approach
A complete MSC programme requires more than expansion
Defined Source
Tissue origin, donor information, collection and traceability should be documented.
Controlled Manufacturing
Culture media, passage limits, environmental conditions and processing steps should be defined.
Product Characterisation
Identity, viability, purity, microbiological safety and functional characteristics should be reviewed together.
Responsible Clinical Translation
The specific preparation must be evaluated in relation to the diagnosis, evidence, route of administration and individual patient.
Selected Scientific References
Foundational MSC terminology and characterisation
Dominici M, et al. Minimal criteria for defining multipotent mesenchymal stromal cells.
Cytotherapy. 2006;8(4):315–317.
View publicationHorwitz EM, et al. Clarification of the nomenclature for MSC.
Cytotherapy. 2005;7(5):393–395.
View publicationViswanathan S, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy position statement on MSC nomenclature.
Cytotherapy. 2019;21(10):1019–1024.
View publicationSensebé L, et al. Clinical-grade production of mesenchymal stem cells.
Bio-Medical Materials and Engineering. 2008;18(Suppl 1):S3–S10.
View publication
Scientific Information
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