Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Advanced Therapy Medicinal Product
4.3. Quality Control
4.3.1. UC-MSC Surface Marker Expression, Cell Viability, and Immunogenicity
4.3.2. Cell Differentiation
4.3.3. Microbiological Tests
4.3.4. Purity Test
4.3.5. Genomic Stability
4.3.6. Cytokinesis-Block Micronucleus Assay
4.3.7. Soft Agar Colony Formation Assay
4.3.8. Potency Test—Inhibition of T-Lymphocyte Proliferation Assay
4.3.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Process | Quality Controls | Methods | Acceptance Criteria | Reference |
---|---|---|---|---|
UC donor selection | Screening | N/A | Eligible donor |
|
Serology for HBV, HCV, HIV, HTLV, Treponema pallidum and Trypanossoma cruzi | Serology and nucleic acid detection | Negative |
| |
UC isolation | Sterility | Automated growth-based | Absence of bacterial or fungal growth |
|
UC-MSC expansion | Adherence to plastic | Microscope observation | Adherent |
|
Viability | Flow cytometry | ≥70% |
| |
Phenotypic markers | Flow cytometry | ≥95% for CD90, CD105, CD73, CD29 and ≤2% for CD14, CD19, CD34, CD45, HLA-DR |
| |
Immunogenicity | Flow cytometry | ≥90% for HLA-ABC ≤2% for CD40, CD80, CD86, HLA-DR | N/A | |
Differential potential assay | Cell differentiation assay | Differentiate into osteoblasts, adipocytes and chondroblasts |
| |
Sterility | Automated growth-based | Absence of bacterial or fungal growth |
| |
Genomic stability | G-Banding Technique | Absence clonal chromosomal alterations |
| |
Potency | Inhibition of T-lymphocyte proliferation assay | Concentration 1:10 (PBMC:MSC) ≥ 50% | N/A | |
Genotoxicity | Cytokinesis-block micronucleus assay | No significantly DNA damage events | N/A | |
Tumorigenicity | Soft agar colony formation assay | Non-tumorigenic | N/A | |
UC-MSC final product | Adherence to plastic | Microscope observation | Adherent cells |
|
Viability | Flow cytometry | ≥70% |
| |
Phenotypic markers | Flow cytometry | ≥95% for CD90, CD105, CD73, CD29 and ≤2% for CD14, CD19, CD34, CD45, HLA-DR |
| |
Procoagulant tissue factor (TF) | Flow cytometry | N/A | N/A | |
Sterility | Automated growth-based | Absence of bacterial or fungal growth |
| |
Mycoplasma | PCR-based and bioluminescent assays | Not detected |
| |
Purity | Chromogenic kinetic | <0.5 EU/mL |
| |
Genomic stability | G-Banding Technique | Absence clonal chromosomal alterations |
|
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Rebelatto, C.L.K.; Boldrini-Leite, L.M.; Daga, D.R.; Marsaro, D.B.; Vaz, I.M.; Jamur, V.R.; de Aguiar, A.M.; Vieira, T.B.; Furman, B.P.; Aguiar, C.O.; et al. Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development. Int. J. Mol. Sci. 2023, 24, 12955. https://doi.org/10.3390/ijms241612955
Rebelatto CLK, Boldrini-Leite LM, Daga DR, Marsaro DB, Vaz IM, Jamur VR, de Aguiar AM, Vieira TB, Furman BP, Aguiar CO, et al. Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development. International Journal of Molecular Sciences. 2023; 24(16):12955. https://doi.org/10.3390/ijms241612955
Chicago/Turabian StyleRebelatto, Carmen Lúcia Kuniyoshi, Lidiane Maria Boldrini-Leite, Debora Regina Daga, Daniela Boscaro Marsaro, Isadora May Vaz, Valderez Ravaglio Jamur, Alessandra Melo de Aguiar, Thalita Bastida Vieira, Bianca Polak Furman, Cecília Oliveira Aguiar, and et al. 2023. "Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development" International Journal of Molecular Sciences 24, no. 16: 12955. https://doi.org/10.3390/ijms241612955