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Quality Control

Standardized assays for cell characterization, purity assessment, and batch consistency in MenSC research and manufacturing.

QC Overview

Quality control is essential for ensuring reproducibility, safety, and efficacy in stem cell research. Our QC program encompasses identity, purity, potency, and safety testing at multiple stages of the manufacturing process.

Identity Confirm cell type
Purity Assess contaminants
Potency Measure function
Safety Detect pathogens
Stability Shelf life data
Consistency Batch-to-batch

Identity Testing

Morphological Assessment

MenSCs exhibit characteristic fibroblast-like morphology with spindle-shaped appearance. Cells should be adherent and form uniform monolayers at confluence.

Acceptance Criteria

  • Spindle-shaped, fibroblastic morphology
  • Adherent growth pattern
  • No signs of differentiation or transformation
  • Uniform cell size (15-30 μm diameter)

Method: Phase contrast microscopy at 10× and 20× magnification

Frequency: Every passage

Immunophenotyping (Flow Cytometry)

Flow cytometry is the gold standard for MSC identification according to ISCT criteria. A minimum panel of markers is required for characterization.

Marker Expected Result Acceptance Criteria Clinical Significance
CD73 Positive ≥95% Ectonucleotidase activity
CD90 Positive ≥95% Thy-1, cell adhesion
CD105 Positive ≥95% Endoglin, TGF-β signaling
CD34 Negative ≤2% Hematopoietic progenitor
CD45 Negative ≤2% Leukocyte common antigen
HLA-DR Negative ≤2% MHC Class II
View Flow Cytometry Protocol →

Differentiation Potential (Functional Identity)

Trilineage differentiation confirms the multipotent nature of MSCs. Cells must demonstrate capacity for osteogenic, adipogenic, and chondrogenic differentiation.

Trilineage Differentiation Panel

Lineage Staining Method Positive Marker Timeline
Osteogenic Alizarin Red S Calcium deposition 14-21 days
Adipogenic Oil Red O Lipid droplets 14-21 days
Chondrogenic Alcian Blue / Safranin O Proteoglycans 21-28 days

Frequency: Per batch (master cell bank)

Purity Assessment

Microbial Contamination

Test Method Acceptance Criteria Frequency
Sterility USP <71> (14-day culture) No growth Final product
Mycoplasma PCR or culture method Negative Master/working cell bank
Endotoxin LAL chromogenic assay <0.5 EU/mL Final product

Viability

Viability Assessment Methods

Trypan Blue Exclusion (Routine): Quick assessment of membrane integrity. Minimum acceptable viability: ≥90% at cryopreservation, ≥85% post-thaw.

Flow Cytometry (Detailed): 7-AAD or PI staining for dead cell discrimination. Provides more accurate quantification and can be combined with immunophenotyping.

Metabolic Assays: MTT, XTT, or alamarBlue for functional viability assessment.

Frequency: Pre/post cryopreservation

Karyotype Analysis

G-banding karyotyping is performed on master cell banks to detect chromosomal abnormalities. Normal diploid karyotype (46,XX for female donors) is required.

Chromosomal Abnormalities to Screen For

  • Aneuploidy (abnormal chromosome number)
  • Structural rearrangements (translocations, deletions)
  • Marker chromosomes
  • Tetraploidy/polyploidy

Acceptance: Normal diploid karyotype in ≥20 metaphase spreads

Frequency: Master cell bank only

Potency Assays

Potency assays measure the specific biological activity of the cell product. For MSCs, immunomodulatory function is the primary mechanism of action for many therapeutic indications.

Immunosuppression Assay

MLR (Mixed Lymphocyte Reaction) Suppression

Principle: Measure ability of MenSCs to suppress T-cell proliferation in a mixed lymphocyte reaction.

Method:

  1. Isolate PBMCs from two unrelated donors
  2. Stimulate with mitogen (PHA) or allogeneic antigen
  3. Add MenSCs at various ratios (1:1 to 1:100)
  4. Measure T-cell proliferation (³H-thymidine or CFSE)

Acceptance: ≥50% suppression of T-cell proliferation at 1:10 ratio

Frequency: Per batch

IDO Activity Assay

Indoleamine 2,3-dioxygenase (IDO) is a key immunosuppressive enzyme upregulated by MSCs in response to IFN-γ. Activity is measured by tryptophan depletion and kynurenine production.

Angiogenesis Assay

Tube Formation Assay

Principle: Assess pro-angiogenic potential by measuring endothelial cell tube formation on Matrigel.

Method: HUVECs plated on Matrigel with MenSC-conditioned media. Quantify total tube length, branch points, and mesh area.

Acceptance:>/strong> ≥2-fold increase in tube formation vs. control media

Batch Release Testing

Pre-Release QC Checklist

Identity: Morphology confirmed normal
Identity: Flow cytometry markers within specification
Purity: Viability ≥85% post-thaw
Safety: Sterility test negative (14-day)
Safety: Endotoxin <0.5 EU/mL
Potency: MLR suppression ≥50%
Documentation: Chain of custody complete