Scalability of spheroid-derived small extracellular vesicles production in stirred systems
Generation of spheroids in a chemically defined medium allowed the culture of highly viable cells in suspension in stirred systems. Spheroid size depended on the system's volumetric power input (P/V), and maintaining this parameter constant during scale-up proved to be the optimal strategy for standardizing the process. However, transferring the spinner flask (SpF) process to the Ambr®250 STBr at constant P/V modified spheroid size, due to important geometric differences and impeller design. Compared to a monolayer reference process, sEV yield decreased two-fold in SpF, but increased two-fold in STBr. Additionally, a lower expression of the CD63 tetraspanin was observed in sEV produced in both stirred systems, suggesting a reduced release of exosomes compared to ectosomes. This study addresses the main issues encountered in spheroid culture scale-up in stirred systems, rather conducive for the production of ectosomes.
Authors
- Julie Hervé (ORCID: https://orcid.org/0000-0001-9735-5518)
- Éric Olmos (ORCID: https://orcid.org/0000-0001-9063-0855)
- Jean‐Marie Bach (ORCID: https://orcid.org/0000-0002-5265-8854)
- Mathilde Mosser (ORCID: https://orcid.org/0000-0003-3556-292X)
- Aurélien Dupont (ORCID: https://orcid.org/0000-0002-3947-0806)
- Laurence de Beaurepaire (ORCID: https://orcid.org/0000-0001-5150-5410)
- Karine Haurogné
- Sophie Sourice
- Apolline Salama (ORCID: https://orcid.org/0000-0002-3157-0749)
- Steffi Bösch (ORCID: https://orcid.org/0000-0002-0995-2775)
- Blandine Lieubeau (ORCID: https://orcid.org/0000-0002-1434-1506)
- Quentin Pruvost
- Thibaud Dauphin (ORCID: https://orcid.org/0009-0002-5085-9668)
- Clémentine Claire
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Laboratoire Réactions et Génie des Procédés (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Oniris (FR)
- Structure Fédérative de Recherche en Biologie et Santé de Rennes (FR)
- Université de Rennes (FR)
- Université de Lorraine (FR)
Publication Details
- Journal
- Frontiers in Bioengineering and Biotechnology
- Published
- 2025-04-29
- DOI
- https://doi.org/10.3389/fbioe.2025.1516482
- Citations
- 3
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Agence Nationale de la Recherche
- Conseil Régional des Pays de la Loire