CHAPTER 12. Standardization and Commercialization of Extracellular Vesicles

Harnessing Nature’s nanoSecrets: biocompatibility, biodistribution and bioactivity of extracellular vesicles derived from microalgae

“…Supporting Table 1 shows that there was not significant body weight loss, indicating that nanoalgosome administration was welltolerated by the animals. Our results demonstrate that a single dose of up to 2x10 11 nanoalgosomes per mouse did not elicit any noticeable immune response or local and systemic toxicity in immune-competent BALB/c mice, allowing for dose escalation or repeated administrations. This is in line with our C. elegans results and with previously published data on I.V.…”

“…dose of EVs in mice corresponds to 55 µg/mouse 30,31 . Thus, in our pre-clinical studies we used the following doses: Dose 1 (low dose) = 10 µg, corresponding to 4x10 10 EVs/mouse; Dose 2 (high dose) = 50 µg, corresponding to 2x10 11 EVs/mouse. Table 1 shows no changes in total white blood cells compared to the normal range, and no alterations in red blood cell counts, hemoglobin, or hematocrit were observed.…”

“…In recent years, there has been growing interest in EVs derived from human mesenchymal stem cells (MSC) 8,9 . However, as MSC-EV manufacturing has turned out to be neither sustainable and controllable, nor economically and environmentally viable, the academic and industrial communities have been exploring alternative approaches to source EVs from other biological sources, such as milk, bacteria, and plants [10][11][12][13][14] . Among these, plant-derived vesicles are currently considered biocompatible, sustainable, and green nanocarriers for the potential development of cancer therapies 14 .…”

Large‐scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop

“…To better manage sources of variability during EV manufacturing and, consequently, increase the safety and bioactivity of the EV products, learning from QbD and safety-by-design approaches has been proposed to the EV community. These approaches require an in-depth understanding of process parameters but provide exciting opportunities opened up by the "design space" (Lipsitz et al, 2016;Zarovni et al, 2022), which allows for process modification within predefined ranges of critical parameters.…”

Quality Management Tools on the Stage: Old but New Allies for Rigor and Standardization of Extracellular Vesicle Studies

“…Interestingly, EVs are a promising source of new biomarkers for liquid biopsy to be used in the diagnosis, prognosis and treatment of different pathologies, including cancer, immune, inflammatory, cardiovascular and neurodegenerative diseases ( Kalluri and LeBleu, 2020 ; Lin et al, 2020 ; Tamura et al, 2021 ; Vozel et al, 2021 ). Moreover, EVs definitely are a valid alternative to synthetic nanocarriers for drug delivery and for the development of pioneering new therapeutic approaches ( Zipkin, 2019 ; Zarovni et al, 2021 ).…”