Technological advances towards extracellular vesicles mass production.

Extracellular vesicles (EVs) are becoming essential actors in bio-therapeutics, as much for their regenerative or immunomodulatory properties as for their potential as cargo delivery vehicles. To enable the democratization of these EV-based therapies, many challenges remain such as large-scale production which is necessary to reduce costs of treatment. Herein, we review some advanced works on high-yield EV manufacturing. One approach consists in developing large-scale cell culture platforms, while others focus on cell stimulation to increase particle yield per cell. This can be done by moderate physico-chemical stresses or by disrupting cell membrane towards autoassembled vesicle-like particles. We critically compare these different techniques, keeping in mind that the field still lacks shared characterization standards, underline the importance of therapeutic potency assessment and discuss mass production strategies that have been identified in current clinical trials.