Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome
MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.918565/full |
| _version_ | 1818210087340081152 |
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| author | Maria Eugenia Fernández-Santos Maria Eugenia Fernández-Santos Mariano Garcia-Arranz Mariano Garcia-Arranz Enrique J. Andreu Enrique J. Andreu Ana Maria García-Hernández Ana Maria García-Hernández Miriam López-Parra Miriam López-Parra Eva Villarón Eva Villarón Pilar Sepúlveda Pilar Sepúlveda Francisco Fernández-Avilés Francisco Fernández-Avilés Damian García-Olmo Damian García-Olmo Felipe Prosper Felipe Prosper Fermin Sánchez-Guijo Fermin Sánchez-Guijo Jose M. Moraleda Jose M. Moraleda Agustin G. Zapata Agustin G. Zapata |
| author_facet | Maria Eugenia Fernández-Santos Maria Eugenia Fernández-Santos Mariano Garcia-Arranz Mariano Garcia-Arranz Enrique J. Andreu Enrique J. Andreu Ana Maria García-Hernández Ana Maria García-Hernández Miriam López-Parra Miriam López-Parra Eva Villarón Eva Villarón Pilar Sepúlveda Pilar Sepúlveda Francisco Fernández-Avilés Francisco Fernández-Avilés Damian García-Olmo Damian García-Olmo Felipe Prosper Felipe Prosper Fermin Sánchez-Guijo Fermin Sánchez-Guijo Jose M. Moraleda Jose M. Moraleda Agustin G. Zapata Agustin G. Zapata |
| author_sort | Maria Eugenia Fernández-Santos |
| collection | DOAJ |
| description | MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs. |
| first_indexed | 2024-12-12T05:11:02Z |
| format | Article |
| id | doaj.art-859113e2a67f49de8a632985ba59dbc7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T05:11:02Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-859113e2a67f49de8a632985ba59dbc72022-12-22T00:36:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.918565918565Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic OutcomeMaria Eugenia Fernández-Santos0Maria Eugenia Fernández-Santos1Mariano Garcia-Arranz2Mariano Garcia-Arranz3Enrique J. Andreu4Enrique J. Andreu5Ana Maria García-Hernández6Ana Maria García-Hernández7Miriam López-Parra8Miriam López-Parra9Eva Villarón10Eva Villarón11Pilar Sepúlveda12Pilar Sepúlveda13Francisco Fernández-Avilés14Francisco Fernández-Avilés15Damian García-Olmo16Damian García-Olmo17Felipe Prosper18Felipe Prosper19Fermin Sánchez-Guijo20Fermin Sánchez-Guijo21Jose M. Moraleda22Jose M. Moraleda23Agustin G. Zapata24Agustin G. Zapata25Cardiology Department, HGU Gregorio Marañón. GMP-ATMPs Production Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM). Complutense University, CIBER Cardiovascular (CIBERCV), ISCIII, Madrid, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainNew Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD). Surgery Department, Autonoma University of Madrid, Madrid, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainHematology Department and Cell Therapy Area, Clínica Universidad de Navarra. CIBEROC and IDISNA, Pamplona, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainHematopoietic Transplant and Cellular Therapy Unit, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainCell Therapy Area and Hematology Department, IBSAL-University Hospital of Salamanca, University of Salamanca, Salamanca, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainCell Therapy Area and Hematology Department, IBSAL-University Hospital of Salamanca, University of Salamanca, Salamanca, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainRegenerative Medicine and Heart Transplantation Unit, Instituto de Investigación Sanitaria La Fe, Valencia, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainCardiology Department, HGU Gregorio Marañón. GMP-ATMPs Production Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM). Complutense University, CIBER Cardiovascular (CIBERCV), ISCIII, Madrid, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainNew Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD). Surgery Department, Autonoma University of Madrid, Madrid, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainHematology Department and Cell Therapy Area, Clínica Universidad de Navarra. CIBEROC and IDISNA, Pamplona, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainCell Therapy Area and Hematology Department, IBSAL-University Hospital of Salamanca, University of Salamanca, Salamanca, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainHematopoietic Transplant and Cellular Therapy Unit, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Virgen de la Arrixaca University Hospital, University of Murcia, Murcia, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainDepartment of Cell Biology, Complutense University, Madrid, SpainPlatform GMP Units from TerCel and TERAV Networks. RETIC TerCel & RICORS TERAV, ISCIII, Madrid, SpainMSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.https://www.frontiersin.org/articles/10.3389/fimmu.2022.918565/fullMSCsATMPslegal requirementsGMP manufacturingextracellular vesicles |
| spellingShingle | Maria Eugenia Fernández-Santos Maria Eugenia Fernández-Santos Mariano Garcia-Arranz Mariano Garcia-Arranz Enrique J. Andreu Enrique J. Andreu Ana Maria García-Hernández Ana Maria García-Hernández Miriam López-Parra Miriam López-Parra Eva Villarón Eva Villarón Pilar Sepúlveda Pilar Sepúlveda Francisco Fernández-Avilés Francisco Fernández-Avilés Damian García-Olmo Damian García-Olmo Felipe Prosper Felipe Prosper Fermin Sánchez-Guijo Fermin Sánchez-Guijo Jose M. Moraleda Jose M. Moraleda Agustin G. Zapata Agustin G. Zapata Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome Frontiers in Immunology MSCs ATMPs legal requirements GMP manufacturing extracellular vesicles |
| title | Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome |
| title_full | Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome |
| title_fullStr | Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome |
| title_full_unstemmed | Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome |
| title_short | Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome |
| title_sort | optimization of mesenchymal stromal cell msc manufacturing processes for a better therapeutic outcome |
| topic | MSCs ATMPs legal requirements GMP manufacturing extracellular vesicles |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.918565/full |
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