摘要

Objectives: Extracellular vesicles (EV) have a high potential in regenerative / anti-aging therapies. Nevertheless, their access to the market in medicine and cosmetics is jeopardized by challenges in the manufacturing methods : the existing methods are limited to small scale, are time consuming, costly, and lack of batch to batch consistency. Manufacturing issues are one of the reasons explaining why human derived EVs are not yet authorized in the european cosmetic market. EVerZom was founded to overcome these issues using a disruptive technology allowing a massive, clinical grade, EV production Introduction: Extracellular Vesicles (EVs) are nanoparticles naturally released from every cells and delimited by a lipid bilayer. EVs are present in many body fluids to transport molecular components from cell to cell. These entities keep the properties of their parent-cells, do not replicate or differentiate and exhibit low immunogenicity. They represent one of the most innovative alternatives to cell-therapy in regenerative medicine. Materials / method: However, their production process is currently mostly limited to small-scale production and does not comply with clinical research regulations. The rare manufacturing methods of batches containing huge amount of EVs are time consuming and costly. The capital challenge to the clinical distribution of EVs remains an industrial scale production to provide sufficient and reproducible quantities of EVs in order to treat a significant number of patients during clinical trials. Among the companies seeking to offer their services in this domain, EVerZom stands out for its innovative production process Results: In collaboration with the Matière et Systèmes Complexes laboratory, EVerZom has developed a disruptive and patented technology to overcome these hurdles. This scalable process boosts EV release by exerting a controlled mechanical stimulation, through a turbulent flow, on a large number of cells during their 3D culture in bioreactors. The yield with this process is 10 times more vesicles in 20 times less time than traditional starvation process. For instance, in 4 hours, every hASC cell in a bioreactor can produce 25,000 small EVs. The cell viability, emain above 90% at the end of the process. Conclusion: These EVs are produced within a culture media free of any chemical agents and animal proteins, limiting the risk of contamination. The secretome produced is characterized all along the process in terms of identity, immunomodulation and regenerative capacities with in vitro assays. The ambition of EVerZom is to produce clinical grade/GMP small EVs to develop therapies as effective as cell therapies for tissue regeneration, diseases such as stroke, heart failure, arthritis while being safer and more convenient for supply chains.