Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development
Mesenchymal stromal cells (MSCs) have been considered a therapeutic strategy in regenerative medicine because of their regenerative and immunomodulatory properties. The translation of MSC-based products has some challenges, such as regulatory and scientific issues. Quality control should be standard...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12955 |
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| author | Carmen Lúcia Kuniyoshi Rebelatto 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 Paulo Roberto Slud Brofman |
| author_facet | Carmen Lúcia Kuniyoshi Rebelatto 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 Paulo Roberto Slud Brofman |
| author_sort | Carmen Lúcia Kuniyoshi Rebelatto |
| collection | DOAJ |
| description | Mesenchymal stromal cells (MSCs) have been considered a therapeutic strategy in regenerative medicine because of their regenerative and immunomodulatory properties. The translation of MSC-based products has some challenges, such as regulatory and scientific issues. Quality control should be standardized and optimized to guarantee the reproducibility, safety, and efficacy of MSC-based products to be administered to patients. The aim of this study was to develop MSC-based products for use in clinical practice. Quality control assays include cell characterization, cell viability, immunogenicity, and cell differentiation; safety tests such as procoagulant tissue factor (TF), microbiological, mycoplasma, endotoxin, genomic stability, and tumorigenicity tests; and potency tests. The results confirm that the cells express MSC markers; an average cell viability of 96.9%; a low expression of HLA-DR and costimulatory molecules; differentiation potential; a high expression of TF/CD142; an absence of pathogenic microorganisms; negative endotoxins; an absence of chromosomal abnormalities; an absence of genotoxicity and tumorigenicity; and T-lymphocyte proliferation inhibition potential. This study shows the relevance of standardizing the manufacturing process and quality controls to reduce variability due to the heterogeneity between donors. The results might also be useful for the implementation and optimization of new analytical techniques and automated methods to improve safety, which are the major concerns related to MSC-based therapy. |
| first_indexed | 2024-03-10T23:51:49Z |
| format | Article |
| id | doaj.art-ca95b62ae5624f10b6823a408edaf753 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:51:49Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ca95b62ae5624f10b6823a408edaf7532023-11-19T01:32:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161295510.3390/ijms241612955Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product DevelopmentCarmen Lúcia Kuniyoshi Rebelatto0Lidiane Maria Boldrini-Leite1Debora Regina Daga2Daniela Boscaro Marsaro3Isadora May Vaz4Valderez Ravaglio Jamur5Alessandra Melo de Aguiar6Thalita Bastida Vieira7Bianca Polak Furman8Cecília Oliveira Aguiar9Paulo Roberto Slud Brofman10Core for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilLaboratory of Basic Biology of Stem Cells, Carlos Chagas Institute—Fiocruz-Paraná, Curitiba 81350-010, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilCore for Cell Technology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba 80215-901, BrazilMesenchymal stromal cells (MSCs) have been considered a therapeutic strategy in regenerative medicine because of their regenerative and immunomodulatory properties. The translation of MSC-based products has some challenges, such as regulatory and scientific issues. Quality control should be standardized and optimized to guarantee the reproducibility, safety, and efficacy of MSC-based products to be administered to patients. The aim of this study was to develop MSC-based products for use in clinical practice. Quality control assays include cell characterization, cell viability, immunogenicity, and cell differentiation; safety tests such as procoagulant tissue factor (TF), microbiological, mycoplasma, endotoxin, genomic stability, and tumorigenicity tests; and potency tests. The results confirm that the cells express MSC markers; an average cell viability of 96.9%; a low expression of HLA-DR and costimulatory molecules; differentiation potential; a high expression of TF/CD142; an absence of pathogenic microorganisms; negative endotoxins; an absence of chromosomal abnormalities; an absence of genotoxicity and tumorigenicity; and T-lymphocyte proliferation inhibition potential. This study shows the relevance of standardizing the manufacturing process and quality controls to reduce variability due to the heterogeneity between donors. The results might also be useful for the implementation and optimization of new analytical techniques and automated methods to improve safety, which are the major concerns related to MSC-based therapy.https://www.mdpi.com/1422-0067/24/16/12955good manufacturing practiceadvanced therapy medicinal productumbilical cord |
| spellingShingle | Carmen Lúcia Kuniyoshi Rebelatto 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 Paulo Roberto Slud Brofman Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development International Journal of Molecular Sciences good manufacturing practice advanced therapy medicinal product umbilical cord |
| title | Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development |
| title_full | Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development |
| title_fullStr | Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development |
| title_full_unstemmed | Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development |
| title_short | Quality Control Optimization for Minimizing Security Risks Associated with Mesenchymal Stromal Cell-Based Product Development |
| title_sort | quality control optimization for minimizing security risks associated with mesenchymal stromal cell based product development |
| topic | good manufacturing practice advanced therapy medicinal product umbilical cord |
| url | https://www.mdpi.com/1422-0067/24/16/12955 |
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