title: Extracellular vesicles concentration is a promising and important parameter for industrial bioprocess monitoring.
abstract: Extracellular vesicles (EVs) are membrane vesicles that are produced by cells to be released into their microenvironment. In this study, we present the EV concentration as a new factor for optimization of industrial bioprocess control. The release of EVs depends on many cell properties, including cell activation and stress status, and cell death. Therefore, the EV concentration might provide a readout for identification of the cell state and the conditions during a bioprocess. Our data show that the EV concentration increased during the bioprocess, which indicated deteriorating conditions in the bioreactor. This increase in EV concentration in the fermentation broth was the consequence of two different processes: cell activation, and cell death. However, the release of EVs from activated living cells had a much weaker impact on EV concentration in the bioreactor than those released during cell death. EVs and cells in the bioprocess environment were quantified by flow cytometry. The most accurate data were obtained directly from unprocessed samples, making the monitoring of the EV concentration a rapid, easy, and cheap method. These EV concentrations reflect the conditions in the bioreactor and provide new information regarding the state of the bioprocess. Therefore, we suggest EV concentration as a new and important parameter for the monitoring of industrial bioprocesses.
authors.affiliation: Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia. polona.bedina@ki.si.
authors.forename: Apolonija Bedina
authors.initials: AB
authors.lastname: Zavec
authors.affiliation: Biomedical Research Group, Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kralj-Iglič
authors.affiliation: Sandoz Biopharmaceuticals-Lek Pharmaceuticals d.d., Mengeš, Slovenia.
authors.forename: Matjaž
authors.initials: M
authors.lastname: Brinc
authors.affiliation: Sandoz Biopharmaceuticals-Lek Pharmaceuticals d.d., Mengeš, Slovenia.
authors.forename: Tanja Ficko
authors.initials: TF
authors.lastname: Trček
authors.affiliation: Sandoz Biopharmaceuticals-Lek Pharmaceuticals d.d., Mengeš, Slovenia.
authors.forename: Drago
authors.initials: D
authors.lastname: Kuzman
authors.affiliation: Sandoz Biopharmaceuticals-Lek Pharmaceuticals d.d., Mengeš, Slovenia.
authors.forename: Ana
authors.initials: A
authors.lastname: Schweiger
authors.affiliation: Laboratory for Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Ljubljana, Slovenia.
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D061249:Batch Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D019149:Bioreactors; D016466:CHO Cells; D049109:Cell Proliferation; D002470:Cell Survival; D060833:Cellular Microenvironment; D003412:Cricetulus; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005434:Flow Cytometry
chemical_list: D000911:Antibodies, Monoclonal
keywords: Cell activation; Cell death; Extracellular vesicles (EV) concentration; Industrial bioprocess; Microenvironment