Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells
Background Cell-based therapies are emerging as a viable modality to treat challenging diseases, resulting in an increasing demand for their large-scale, high-quality production. Production facilities face the issue of batch-to-batch consistency while producing a safe and efficient cell-based produc...
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| Format: | Article |
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PeerJ Inc.
2022-05-01
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| Online Access: | https://peerj.com/articles/13391.pdf |
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| author | Clotilde Aussel Elodie Busson Helene Vantomme Juliette Peltzer Christophe Martinaud |
| author_facet | Clotilde Aussel Elodie Busson Helene Vantomme Juliette Peltzer Christophe Martinaud |
| author_sort | Clotilde Aussel |
| collection | DOAJ |
| description | Background Cell-based therapies are emerging as a viable modality to treat challenging diseases, resulting in an increasing demand for their large-scale, high-quality production. Production facilities face the issue of batch-to-batch consistency while producing a safe and efficient cell-based product. Controlling culture conditions and particularly media composition is a key factor of success in this challenge. Serum and Xeno-Free Media (SXFM) represent an interesting option to achieve this goal. By reducing batch to batch variability, they increase Good Manufacturing Practices (GMP)-compliance and safety regarding xenogenic transmission, as compared to fetal bovine serum (FBS) supplemented-media or human platelet lysate supplemented medium. Methods In this study, the isolation, expansion and characteristics including the anti-inflammatory function of human mesenchymal stromal cells (MSC) are compared after culture in MEMα supplemented with human Concentrate Platelet Lysate (hCPL, reference medium) or in MSC-Brew GMP Medium. The latter is a GMP SXFM manufactured in bags under strictly controlled conditions in volumes suitable for expansion to a clinical scale and does not require neither pre-coating of the cell culture units nor the addition of blood derivatives at the isolation step. Results We showed that MSC derived from human bone-marrow and adipose tissue can be successfully isolated and expanded in this SXFM. Number and size of Colony-Forming Unit fibroblast (CFU-F) is increased compared to cells cultivated in hCPL medium. All cells retained a CD90+, CD73+, CD105+, HLADR−, CD34−, CD45− phenotype. Furthermore, the osteogenic and adipocyte potentials as well as the anti-inflammatory activity were comparable between culture conditions. All cells reached the release criteria established in our production facility to treat inflammatory pathologies. Conclusions The use of MSC-Brew GMP Medium can therefore be considered for clinical bioprocesses as a safe and efficient substitute for hCPL media. |
| first_indexed | 2024-03-09T06:42:30Z |
| format | Article |
| id | doaj.art-89c490c3d25d4f348870176cc0686fff |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:42:30Z |
| publishDate | 2022-05-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-89c490c3d25d4f348870176cc0686fff2023-12-03T10:48:11ZengPeerJ Inc.PeerJ2167-83592022-05-0110e1339110.7717/peerj.13391Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cellsClotilde Aussel0Elodie Busson1Helene Vantomme2Juliette Peltzer3Christophe Martinaud4Biomedical Research Institute of the Armed Forces, Clamart, FranceAdvanced Therapy Medicine Unit, French Military Blood Institute, Clamart, FranceAdvanced Therapy Medicine Unit, French Military Blood Institute, Clamart, FranceBiomedical Research Institute of the Armed Forces, Clamart, FranceAdvanced Therapy Medicine Unit, French Military Blood Institute, Clamart, FranceBackground Cell-based therapies are emerging as a viable modality to treat challenging diseases, resulting in an increasing demand for their large-scale, high-quality production. Production facilities face the issue of batch-to-batch consistency while producing a safe and efficient cell-based product. Controlling culture conditions and particularly media composition is a key factor of success in this challenge. Serum and Xeno-Free Media (SXFM) represent an interesting option to achieve this goal. By reducing batch to batch variability, they increase Good Manufacturing Practices (GMP)-compliance and safety regarding xenogenic transmission, as compared to fetal bovine serum (FBS) supplemented-media or human platelet lysate supplemented medium. Methods In this study, the isolation, expansion and characteristics including the anti-inflammatory function of human mesenchymal stromal cells (MSC) are compared after culture in MEMα supplemented with human Concentrate Platelet Lysate (hCPL, reference medium) or in MSC-Brew GMP Medium. The latter is a GMP SXFM manufactured in bags under strictly controlled conditions in volumes suitable for expansion to a clinical scale and does not require neither pre-coating of the cell culture units nor the addition of blood derivatives at the isolation step. Results We showed that MSC derived from human bone-marrow and adipose tissue can be successfully isolated and expanded in this SXFM. Number and size of Colony-Forming Unit fibroblast (CFU-F) is increased compared to cells cultivated in hCPL medium. All cells retained a CD90+, CD73+, CD105+, HLADR−, CD34−, CD45− phenotype. Furthermore, the osteogenic and adipocyte potentials as well as the anti-inflammatory activity were comparable between culture conditions. All cells reached the release criteria established in our production facility to treat inflammatory pathologies. Conclusions The use of MSC-Brew GMP Medium can therefore be considered for clinical bioprocesses as a safe and efficient substitute for hCPL media.https://peerj.com/articles/13391.pdfMesenchymal stromal cellsPlatelet LysateGMP mediumClinical grade productionQuality |
| spellingShingle | Clotilde Aussel Elodie Busson Helene Vantomme Juliette Peltzer Christophe Martinaud Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells PeerJ Mesenchymal stromal cells Platelet Lysate GMP medium Clinical grade production Quality |
| title | Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells |
| title_full | Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells |
| title_fullStr | Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells |
| title_full_unstemmed | Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells |
| title_short | Quality assessment of a serum and xenofree medium for the expansion of human GMP-grade mesenchymal stromal cells |
| title_sort | quality assessment of a serum and xenofree medium for the expansion of human gmp grade mesenchymal stromal cells |
| topic | Mesenchymal stromal cells Platelet Lysate GMP medium Clinical grade production Quality |
| url | https://peerj.com/articles/13391.pdf |
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