{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:44:44Z","timestamp":1785926684513,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016156","name":"Army Medical Research Acquisition Activity","doi-asserted-by":"publisher","award":["W81XWH2210371"],"award-info":[{"award-number":["W81XWH2210371"]}],"id":[{"id":"10.13039\/100016156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016156","name":"Army Medical Research Acquisition Activity","doi-asserted-by":"publisher","award":["W81XWH2210656"],"award-info":[{"award-number":["W81XWH2210656"]}],"id":[{"id":"10.13039\/100016156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014008","name":"Ovarian Cancer Research Alliance Collaborative Research Development Grant","doi-asserted-by":"publisher","award":["GR143575"],"award-info":[{"award-number":["GR143575"]}],"id":[{"id":"10.13039\/100014008","id-type":"DOI","asserted-by":"publisher"}]},{"award":["GR143575"],"award-info":[{"award-number":["GR143575"]}],"id":[{"id":"https:\/\/ror.org\/05hg41718","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Extracellular vesicles (EVs) from ovarian cancer cells are valuable sources for candidate biomarker studies, but conventional static flask culture yields limited material and is difficult to scale reproducibly. We evaluated a serum-free CELLine AD 1000 bioreactor workflow for producing EVs from four ovarian cancer-related (OC-related) cell lines (OVCAR4, CaOV3, PA1, SW626) and human dermal fibroblasts (HDFa) as a non-cancer control. Cells were adapted to CDM-HD serum-free medium and maintained for eight weeks with twice-weekly conditioned-medium collection. EVs were isolated by differential ultracentrifugation followed by size-exclusion chromatography and characterized by nanoparticle tracking analysis, imaging flow cytometry, Western blotting, and transmission and scanning electron microscopy. Across longitudinal harvests, OC-related cultures generally produced higher EV particle concentrations and A280-based bulk protein estimates than HDFa, while individual cell lines showed distinct production profiles and membrane-associated growth patterns. A parallel OVCAR4 T-175 flask, maintained in its original serum-containing medium, provided a contextual reference indicating higher per-collection EV particle recovery with the bioreactor, although this was not a matched culture-format comparison. EV-enriched preparations contained vesicle-like particles, with modal diameters of approximately 96\u2013128 nm. Using imaging flow cytometry, the CD9 signal was higher in OC-related EVs and CD63 was most prominent in HDFa; CD9 and CD63 were also detected in OC-related EV lysates by Western blotting. Because one bioreactor was operated per cell line, these findings should be interpreted as preliminary and descriptive rather than statistically comparative. Overall, this study provides a practical serum-free CELLine AD 1000 workflow for generating characterized OC-related EV material for downstream analytical studies.<\/jats:p>","DOI":"10.3390\/bioengineering13080896","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:16:22Z","timestamp":1785921382000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Scalable Bioreactor Platform for Reproducible Production and Characterization of Ovarian Cancer-Derived Extracellular Vesicles"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4581-8909","authenticated-orcid":false,"given":"Wei","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-0874","authenticated-orcid":false,"given":"Kalpana Deepa Priya","family":"Dorayappan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-3600","authenticated-orcid":false,"given":"Colin","family":"Hisey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA"},{"name":"William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-039X","authenticated-orcid":false,"given":"Lakshmi Narasimhan","family":"Chakrapani","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6039-8291","authenticated-orcid":false,"given":"Sydney","family":"Wiggins","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6869-2988","authenticated-orcid":false,"given":"Shyam","family":"Sundaram","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4009-4769","authenticated-orcid":false,"given":"Zachary","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Truc","family":"Nguyen","sequence":"additional","affiliation":[{"name":"William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2784-7751","authenticated-orcid":false,"given":"Sudhiksha Anbu","family":"Chelian","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-8205","authenticated-orcid":false,"given":"Eduardo","family":"Reategui","sequence":"additional","affiliation":[{"name":"William G. 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Clin."},{"key":"ref_2","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1001\/jama.2025.9495","article-title":"Ovarian cancer: A review","volume":"334","author":"Caruso","year":"2025","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17588359241233225","DOI":"10.1177\/17588359241233225","article-title":"Diagnostic biomarkers in ovarian cancer: Advances beyond CA125 and HE4","volume":"16","author":"Ghose","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1001\/jama.2011.766","article-title":"Effect of screening on ovarian cancer mortality: The prostate, lung, colorectal and ovarian (PLCO) cancer screening randomized controlled trial","volume":"305","author":"Buys","year":"2011","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1016\/S0140-6736(21)00731-5","article-title":"Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial","volume":"397","author":"Menon","year":"2021","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/clinchem\/hvad176","article-title":"Extracellular vesicles as liquid biopsy biomarkers across the cancer journey: From early detection to recurrence","volume":"70","author":"Rayamajhi","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.cell.2016.01.043","article-title":"Communication by extracellular vesicles: Where we are and where we need to go","volume":"164","author":"Tkach","year":"2016","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular vesicles as tools and targets in therapy for diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev-genet-111523-102725","article-title":"The Nature and Nurture of Extracellular Vesicle\u2013Mediated Signaling","volume":"58","author":"Buck","year":"2024","journal-title":"Annu. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ygyno.2007.08.064","article-title":"Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM","volume":"107","author":"Runz","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Skryabin, G.O., Komelkov, A.V., Zhordania, K.I., Bagrov, D.V., Enikeev, A.D., Galetsky, S.A., Beliaeva, A.A., Kopnin, P.B., Moiseenko, A.V., and Senkovenko, A.M. (2024). Integrated miRNA Profiling of Extracellular Vesicles from Uterine Aspirates, Malignant Ascites and Primary-Cultured Ascites Cells for Ovarian Cancer Screening. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16070902"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120771","DOI":"10.1016\/j.cca.2025.120771","article-title":"Exosomal microRNA biomarkers in ovarian cancer detection: Systematic review and meta-analysis","volume":"584","author":"Huang","year":"2026","journal-title":"Clin. Chim. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120011","DOI":"10.1016\/j.cca.2024.120011","article-title":"Ovarian cancer extracellular vesicle biomarkers","volume":"565","author":"Jamali","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.jmoldx.2024.09.001","article-title":"Improving specificity for ovarian cancer screening using a novel extracellular vesicle\u2013based blood test: Performance in a training and verification cohort","volume":"26","author":"Bortolin","year":"2024","journal-title":"J. Mol. Diagn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12943-024-02103-x","article-title":"Unraveling the extracellular vesicle network: Insights into ovarian cancer metastasis and chemoresistance","volume":"23","author":"Dai","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11150","DOI":"10.1038\/ncomms11150","article-title":"Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1","volume":"7","author":"Co","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s10020-025-01177-7","article-title":"Distinctive features of blood- and ascitic fluid-derived extracellular vesicles in ovarian cancer patients","volume":"31","author":"Gorini","year":"2025","journal-title":"Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e12420","DOI":"10.1002\/jev2.12420","article-title":"Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer","volume":"13","author":"Kravec","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1093\/clinchem\/hvad189","article-title":"Towards the clinical implementation of extracellular vesicle-based biomarker assays for cancer","volume":"70","author":"Tummers","year":"2024","journal-title":"Clin. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20360","DOI":"10.3402\/jev.v2i0.20360","article-title":"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research","volume":"2","author":"Witwer","year":"2013","journal-title":"J. Extracell. Vesicles"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1021\/acs.jproteome.5c00149","article-title":"Comprehensive comparison of methods for isolation of extracellular vesicles from human plasma","volume":"24","author":"Suresh","year":"2025","journal-title":"J. Proteome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbrc.2013.12.070","article-title":"In-depth proteomic analyses of ovarian cancer cell line exosomes reveals differential enrichment of functional categories compared to the NCI 60 proteome","volume":"445","author":"Sinha","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1002\/jex2.60","article-title":"Investigating the consistency of extracellular vesicle production from breast cancer subtypes using CELLine adherent bioreactors","volume":"1","author":"Hisey","year":"2022","journal-title":"J. Extracell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jim.2008.03.001","article-title":"Increased exosome production from tumour cell cultures using the Integra CELLine Culture System","volume":"335","author":"Mitchell","year":"2008","journal-title":"J. Immunol. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e12408","DOI":"10.1002\/jev2.12408","article-title":"Heat inactivation of foetal bovine serum performed after EV-depletion influences the proteome of cell-derived extracellular vesicles","volume":"13","author":"Bergqvist","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12061","DOI":"10.1002\/jev2.12061","article-title":"Foetal bovine serum influence on in vitro extracellular vesicle analyses","volume":"10","author":"Lehrich","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_31","unstructured":"Turksen, K. (2022). Production of Extracellular Vesicles Using a CELLine Adherent Bioreactor Flask. Bioreactors in Stem Cell Biology: Methods and Protocols, Springer."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ng, C.Y., Kee, L.T., Al-Masawa, M.E., Lee, Q.H., Subramaniam, T., Kok, D., Ng, M.H., and Law, J.X. (2022). Scalable production of extracellular vesicles and its therapeutic values: A review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147986"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/j.tibtech.2024.03.010","article-title":"A roadmap towards manufacturing extracellular vesicles for cardiac repair","volume":"42","author":"Louro","year":"2024","journal-title":"Trends Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.biomaterials.2016.07.003","article-title":"Efficient production and enhanced tumor delivery of engineered extracellular vesicles","volume":"105","author":"Watson","year":"2016","journal-title":"Biomaterials"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13287-021-02190-3","article-title":"Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell","volume":"12","author":"Gobin","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Jakl, V., Ehmele, M., Winkelmann, M., Ehrenberg, S., Eiseler, T., Friemert, B., Rojewski, M.T., and Schrezenmeier, H. (2023). A novel approach for large-scale manufacturing of small extracellular vesicles from bone marrow-derived mesenchymal stromal cells using a hollow fiber bioreactor. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1107055"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.20517\/evcna.2023.76","article-title":"Hollow fiber bioreactor allows sustained production of immortalized mesenchymal stromal cell-derived extracellular vesicles","volume":"5","author":"Garcia","year":"2024","journal-title":"Extracell. Vesicles Circ. Nucleic Acids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1530\/REP-22-0215","article-title":"Production of extracellular vesicles from equine embryo-derived mesenchymal stromal cells","volume":"164","author":"Tasma","year":"2022","journal-title":"Reproduction"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s44301-026-00021-z","article-title":"Bioreactor-enabled extracellular vesicle production for downstream functional engineering","volume":"2","author":"Tripp","year":"2026","journal-title":"Health Nanotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/jnci\/91.15.1327","article-title":"Evidence for the colonic origin of ovarian cancer cell line SW626","volume":"91","author":"Furlong","year":"1999","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1038\/s41592-025-02914-w","article-title":"Light-induced extracellular vesicle and particle adsorption","volume":"22","author":"Hisey","year":"2025","journal-title":"Nat. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kowkabany, G., and Bao, Y. (2024). Nanoparticle tracking analysis: An effective tool to characterize extracellular vesicles. Molecules, 29.","DOI":"10.3390\/molecules29194672"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1002\/jex2.115","article-title":"Cell culture-derived extracellular vesicles: Considerations for reporting cell culturing parameters","volume":"2","author":"Shekari","year":"2023","journal-title":"J. Extracell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1038\/s41598-018-22142-x","article-title":"Improved isolation strategies to increase the yield and purity of human urinary exosomes for biomarker discovery","volume":"8","author":"Gheinani","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2401069","DOI":"10.1002\/advs.202401069","article-title":"Extracellular vesicle preparation and analysis: A state-of-the-art review","volume":"11","author":"Wang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1038\/s41467-021-24384-2","article-title":"Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9","volume":"12","author":"Mathieu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Duke, L.C., Cone, A.S., Sun, L., Dittmer, D.P., Meckes, D.G., and Tomko, R.J. (2025). Tetraspanin CD9 alters cellular trafficking and endocytosis of tetraspanin CD63, affecting CD63 packaging into small extracellular vesicles. J. Biol. Chem., 301.","DOI":"10.1016\/j.jbc.2025.108255"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejogrb.2025.01.011","article-title":"CD63 as a potential biomarker for patients with ovarian cancer","volume":"306","author":"Nakamura","year":"2025","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/8\/896\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:58:05Z","timestamp":1785923885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/8\/896"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["bioengineering13080896"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13080896","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}