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Peer-reviewedCC BY 4.0Advanced Science

A Hydrodynamic Bioreactor for High-Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling

Abstract

Extracellular vesicles (EVs) have become pivotal in clinical therapeutics, although no consensus exists on optimal production methods. Here, we introduce an innovative approach and associated device that employs hydrodynamic stress to form and stimulate stem cell spheroids. The method involves culturing cellular material in vessels equipped with internal obstacles, subjected to rotational motion at varying speeds and in alternating reversing modes. It achieves EV yields 10 to 20 times greater than those obtained with traditional static culture methods, offering a robust and scalable solution for EV production. This approach not only streamlines spheroid formation and subsequent EV release into a single, integrated process but also ensures the generation of EVs with enhanced biological activity and a distinctive protein cargo signature. Notably, hydrodynamic stimulation enriched EVs with ectosome-and mitochondria-associated proteins, suggesting distinct biogenesis pathways, while these hydrodynamically-produced EVs demonstrated superior functionality in promoting wound healing, angiogenesis, and antiinflammatory responses, underscoring their therapeutic potential.

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BibTeX
@article{lenoir2026hydrodynamic,
  title = {{A Hydrodynamic Bioreactor for High-Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling}},
  author = {Solène Lenoir and Elliot Thouvenot and Giacomo Gropplero and Léonie Dec and Damarys Loew and Clotilde Théry and Jose Perez and Claire Wilhelm},
  journal = {Advanced Science},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.202510607},
  url = {https://inserm.hal.science/inserm-05779155v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A Hydrodynamic Bioreactor for High-Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling
AU  - Solène Lenoir
AU  - Elliot Thouvenot
AU  - Giacomo Gropplero
AU  - Léonie Dec
AU  - Damarys Loew
AU  - Clotilde Théry
AU  - Jose Perez
AU  - Claire Wilhelm
PY  - 2026
DA  - 2026/10/05
JO  - Advanced Science
DO  - 10.1002/advs.202510607
UR  - https://inserm.hal.science/inserm-05779155v1
AB  - Extracellular vesicles (EVs) have become pivotal in clinical therapeutics, although no consensus exists on optimal production methods. Here, we introduce an innovative approach and associated device that employs hydrodynamic stress to form and stimulate stem cell spheroids. The method involves culturing cellular material in vessels equipped with internal obstacles, subjected to rotational motion at varying speeds and in alternating reversing modes. It achieves EV yields 10 to 20 times greater than those obtained with traditional static culture methods, offering a robust and scalable solution for EV production. This approach not only streamlines spheroid formation and subsequent EV release into a single, integrated process but also ensures the generation of EVs with enhanced biological activity and a distinctive protein cargo signature. Notably, hydrodynamic stimulation enriched EVs with ectosome-and mitochondria-associated proteins, suggesting distinct biogenesis pathways, while these hydrodynamically-produced EVs demonstrated superior functionality in promoting wound healing, angiogenesis, and antiinflammatory responses, underscoring their therapeutic potential.
SN  - 2198-3844
ER  -