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

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Main Authors: Solène Lenoir, Elliot Thouvenot, Giacomo Gropplero, Léonie Dec, Damarys Loew, Clotilde Théry, Jose E Perez, Claire Wilhelm
Format: Artículo Open Access
Published: Wiley 2025
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author Solène Lenoir
Elliot Thouvenot
Giacomo Gropplero
Léonie Dec
Damarys Loew
Clotilde Théry
Jose E Perez
Claire Wilhelm
author_facet Solène Lenoir
Elliot Thouvenot
Giacomo Gropplero
Léonie Dec
Damarys Loew
Clotilde Théry
Jose E Perez
Claire Wilhelm
Solène Lenoir
Elliot Thouvenot
Giacomo Gropplero
Léonie Dec
Damarys Loew
Clotilde Théry
Jose E Perez
Claire Wilhelm
collection Wiley Open Access
contents A Hydrodynamic Bioreactor for High‐Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling Solène Lenoir Elliot Thouvenot Giacomo Gropplero Léonie Dec Damarys Loew Clotilde Théry Jose E Perez Claire Wilhelm Advanced Science Abstract Extracellular vesicles (EVs) have become pivotal in clinical therapeutics, although no consensus exists on optimal production methods. Here, an innovative approach and associated device are introduced that employ 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 high‐output method compatible with large‐scale EV manufacturing. 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. Additionally, these EVs demonstrated superior functionality in promoting wound healing, angiogenesis, and anti‐inflammatory responses, underscoring their therapeutic potential. 10.1002/advs.202510607 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1002/advs.202510607
format Artículo Open Access
id wiley_oa_10_1002_advs_202510607
institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by/4.0/
publishDate 2025
publisher Wiley
record_format wiley_oa
spellingShingle A Hydrodynamic Bioreactor for High‐Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling
Solène Lenoir
Elliot Thouvenot
Giacomo Gropplero
Léonie Dec
Damarys Loew
Clotilde Théry
Jose E Perez
Claire Wilhelm
Advanced Science
A Hydrodynamic Bioreactor for High‐Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling Solène Lenoir Elliot Thouvenot Giacomo Gropplero Léonie Dec Damarys Loew Clotilde Théry Jose E Perez Claire Wilhelm Advanced Science Abstract Extracellular vesicles (EVs) have become pivotal in clinical therapeutics, although no consensus exists on optimal production methods. Here, an innovative approach and associated device are introduced that employ 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 high‐output method compatible with large‐scale EV manufacturing. 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. Additionally, these EVs demonstrated superior functionality in promoting wound healing, angiogenesis, and anti‐inflammatory responses, underscoring their therapeutic potential. 10.1002/advs.202510607 http://creativecommons.org/licenses/by/4.0/
title A Hydrodynamic Bioreactor for High‐Yield Production of Extracellular Vesicles from Stem Cell Spheroids with Defined Cargo Profiling
topic Advanced Science
url https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202510607