Design and validation of a GMP-compliant manufacturing platform of extracellular vesicles from mesenchymal stromal cells
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.
Authors
- Alba López‐Fernández (ORCID: https://orcid.org/0000-0001-6072-0294)
- Marta Tortajada (ORCID: https://orcid.org/0000-0003-2125-0810)
- Sara Morini (ORCID: https://orcid.org/0000-0002-9124-1795)
- Sergi Querol (ORCID: https://orcid.org/0000-0002-1105-8633)
- Antoni Bayes-genis A (ORCID: https://orcid.org/0000-0002-3044-197X)
- Gemma Aran (ORCID: https://orcid.org/0000-0003-2005-8843)
- Santiago Roura (ORCID: https://orcid.org/0000-0003-4063-9661)
- Joaquim Vives (ORCID: https://orcid.org/0000-0001-9719-5235)
- Margarita Codinach (ORCID: https://orcid.org/0000-0003-0560-8798)
- Yvan Courageux (ORCID: https://orcid.org/0000-0002-1484-2677)
- Cristina Prat‐Vidal (ORCID: https://orcid.org/0000-0002-5621-1101)
- Francesc Poblador (ORCID: https://orcid.org/0009-0000-0526-0774)
- Leonie Schoch (ORCID: https://orcid.org/0000-0002-2492-6807)
- Carolina Gálvez‐Montón (ORCID: https://orcid.org/0000-0003-2254-9371)
- Luciano Rodrı́guez
- Silvia Torrents
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Universitat Autònoma de Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Vall d'Hebron Institut de Recerca (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Banc de Sang i Teixits (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- University of Lausanne (CH)
Publication Details
- Journal
- iScience
- Published
- 2026-10-15
- DOI
- https://doi.org/10.1016/j.isci.2026.117881
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministerio de Ciencia, Innovación y Universidades
- European Cooperation in Science and Technology
- Generalitat de Catalunya
- Instituto de Salud Carlos III