Design and validation of a GMP-compliant manufacturing platform of extracellular vesicles from mesenchymal stromal cells
Abstract
There is growing interest in mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as key components in the development of next-generation regenerative cell-free therapies; however, their clinical translation remains limited by a lack of validated clinical-grade manufacturing platforms. Thus, we have established a good manufacturing practice (GMP)-compliant, semi-automated, mid-scale manufacturing workflow that couples the single-use stirred-tank bioreactor expansion of Wharton's jelly-derived MSCs with tangential flow filtration and automated size-exclusion chromatography, featuring in-line monitoring of critical process parameters. The MSC-EV-based product meets pre-specified critical quality attributes (CQAs), co-expresses parental-cell- and EV-specific markers, and complies with standardized quality and safety regulations. Moreover, the final product CQAs-including CD73-associated immunomodulatory activity-remained within acceptable limits for 12 months of storage in PlasmaLyte 148 at -80°C. Overall, our integrated platform yields MSC-EVs with high batch-to-batch reproducibility, in alignment with current GMP and regulatory standards, thereby providing a robust foundation supporting their potential clinical applicability.
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BibTeX
@article{courageux2026design,
title = {{Design and validation of a GMP-compliant manufacturing platform of extracellular vesicles from mesenchymal stromal cells}},
author = {Yvan Courageux and Marta Monguió-Tortajada and Alba López-Fernández and Leonie Schoch and Francesc Poblador and Sara Morini and Cristina Prat-Vidal and Luciano Rodriguez and Silvia Torrents and Gemma Aran and Margarita Codinach and Carolina Gálvez-Montón and Antoni Bayes-Genis and Joaquim Vives and Sergi Querol and Santiago Roura},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117881},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03264-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Design and validation of a GMP-compliant manufacturing platform of extracellular vesicles from mesenchymal stromal cells
AU - Yvan Courageux
AU - Marta Monguió-Tortajada
AU - Alba López-Fernández
AU - Leonie Schoch
AU - Francesc Poblador
AU - Sara Morini
AU - Cristina Prat-Vidal
AU - Luciano Rodriguez
AU - Silvia Torrents
AU - Gemma Aran
AU - Margarita Codinach
AU - Carolina Gálvez-Montón
AU - Antoni Bayes-Genis
AU - Joaquim Vives
AU - Sergi Querol
AU - Santiago Roura
PY - 2026
DA - 2026/10/15
JO - iScience
DO - 10.1016/j.isci.2026.117881
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03264-5
AB - There is growing interest in mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) as key components in the development of next-generation regenerative cell-free therapies; however, their clinical translation remains limited by a lack of validated clinical-grade manufacturing platforms. Thus, we have established a good manufacturing practice (GMP)-compliant, semi-automated, mid-scale manufacturing workflow that couples the single-use stirred-tank bioreactor expansion of Wharton's jelly-derived MSCs with tangential flow filtration and automated size-exclusion chromatography, featuring in-line monitoring of critical process parameters. The MSC-EV-based product meets pre-specified critical quality attributes (CQAs), co-expresses parental-cell- and EV-specific markers, and complies with standardized quality and safety regulations. Moreover, the final product CQAs-including CD73-associated immunomodulatory activity-remained within acceptable limits for 12 months of storage in PlasmaLyte 148 at -80°C. Overall, our integrated platform yields MSC-EVs with high batch-to-batch reproducibility, in alignment with current GMP and regulatory standards, thereby providing a robust foundation supporting their potential clinical applicability.
SN - 2589-0042
ER -