Production of extracellular vesicles from beta cells in stirred tanks enhances maturation and ectosome release with preserved immune properties
Abstract
Small extracellular vesicles (sEVs) derived from beta cells are promising therapeutics for diabetes through their ability to modulate inflammation, preserve pancreatic function, and limit pathogenic mechanisms. For clinical translation, scalable production in a stirred tank bioreactor (STR) is essential, but shear stress can affect sEV function. Here, we report the influence of culture mode, medium formulation, and process parameters on beta cell performance and sEV quality. Small spheroid culture promotes beta cell maturation without affecting sEV yield, whereas stirring increases cellular stress and decreases viability. An optimized three-step bioprocess maximizes cell viability and sEV yields at high cell density in STR over short production periods. The produced sEVs display high purity, preserved membrane integrity, and immunomodulatory activity by reducing T-lymphocyte proliferation and IFN-γ cytokine secretion in an allogenic mixed lymphocyte reaction. Flow cytometry shows enhanced ectosome production in STR, and low glucose medium promotes insulin sorting into beta cell-derived sEVs.
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BibTeX
@article{beaurepaire2026production,
title = {{Production of extracellular vesicles from beta cells in stirred tanks enhances maturation and ectosome release with preserved immune properties}},
author = {Laurence de Beaurepaire and Thibaud Dauphin and Quentin Pruvost and Apolline Salama and Aurelien Dupont and Laurence Dubreil and Grégoire Mignot and Benjamin Mahieu and Julie Hervé and Blandine Lieubeau and Jean-Marie Bach and Steffi Bosch and Mathilde Mosser},
journal = {Cell Reports Physical Science},
year = {2026},
month = jul,
doi = {10.1016/j.xcrp.2026.103391},
url = {https://hal.science/hal-05679366v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Production of extracellular vesicles from beta cells in stirred tanks enhances maturation and ectosome release with preserved immune properties
AU - Laurence de Beaurepaire
AU - Thibaud Dauphin
AU - Quentin Pruvost
AU - Apolline Salama
AU - Aurelien Dupont
AU - Laurence Dubreil
AU - Grégoire Mignot
AU - Benjamin Mahieu
AU - Julie Hervé
AU - Blandine Lieubeau
AU - Jean-Marie Bach
AU - Steffi Bosch
AU - Mathilde Mosser
PY - 2026
DA - 2026/07/15
JO - Cell Reports Physical Science
DO - 10.1016/j.xcrp.2026.103391
UR - https://hal.science/hal-05679366v1
AB - Small extracellular vesicles (sEVs) derived from beta cells are promising therapeutics for diabetes through their ability to modulate inflammation, preserve pancreatic function, and limit pathogenic mechanisms. For clinical translation, scalable production in a stirred tank bioreactor (STR) is essential, but shear stress can affect sEV function. Here, we report the influence of culture mode, medium formulation, and process parameters on beta cell performance and sEV quality. Small spheroid culture promotes beta cell maturation without affecting sEV yield, whereas stirring increases cellular stress and decreases viability. An optimized three-step bioprocess maximizes cell viability and sEV yields at high cell density in STR over short production periods. The produced sEVs display high purity, preserved membrane integrity, and immunomodulatory activity by reducing T-lymphocyte proliferation and IFN-γ cytokine secretion in an allogenic mixed lymphocyte reaction. Flow cytometry shows enhanced ectosome production in STR, and low glucose medium promotes insulin sorting into beta cell-derived sEVs.
SN - 2666-3864
ER -