{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:44:33Z","timestamp":1790948673369,"version":"4.1.0"},"reference-count":85,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["isevjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Extracellular Bio"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Extracellular vesicles (EVs) secreted by human\u2010induced pluripotent stem cells (hiPSCs) have great potential as cell\u2010free therapies in various diseases, including prevention of blood\u2013brain barrier senescence and stroke. However, there are still challenges in pre\u2010clinical and clinical use of hiPSC\u2010EVs due to the need for large\u2010scale production of a large quantity. Vertical\u2010Wheel bioreactors (VWBRs) have design features that allow the biomanufacturing of hiPSC\u2010EVs using a scalable aggregate or microcarrier\u2010based culture system under low shear stress. EV secretion by undifferentiated hiPSCs expanded as 3\u2010D aggregates and on Synthemax II microcarriers in VWBRs were investigated. Additionally, two types of EV collection media, mTeSR and HBM, were compared. The hiPSCs were characterized by metabolite and transcriptome analysis as well as EV biogenesis markers. Protein and microRNA cargo were analysed by proteomics and microRNA\u2010seq, respectively. The\n                    <jats:italic>in vitro<\/jats:italic>\n                    functional assays of microglia stimulation and proliferation were conducted. HiPSCs expanded as 3\u2010D aggregates and on microcarriers had comparable cell number, while microcarrier culture had higher glucose consumption, higher glycolysis and lower autophagy gene expression based on mRNA\u2010seq. The microcarrier cultures had at least 17\u201323 fold higher EV secretion, and EV collection in mTeSR had 2.7\u20133.7 fold higher yield than HBM medium. Microcarrier culture with mTeSR EV collection had a smaller EV size than other groups, and the cargo was enriched with proteins (proteomics) and miRNAs (microRNA\u2010seq) reducing apoptosis and promoting cell proliferation (e.g. Wnt\u2010related pathways). hiPSC\u2010EVs demonstrated the ability of stimulating proliferation and M2 polarization of microglia\n                    <jats:italic>in vitro<\/jats:italic>\n                    . HiPSC expansion on microcarriers produces much higher yields of EVs than hiPSC aggregates in VWBRs. EV collection in mTeSR increases yield compared to HBM. The biomanufactured EVs from microcarrier culture in mTeSR have exosomal characteristics and are functional in microglia stimulation, which paves the ways for future in vivo anti\u2010aging study.\n                  <\/jats:p>","DOI":"10.1002\/jex2.133","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T10:49:15Z","timestamp":1704797355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Extracellular vesicle biogenesis of three\u2010dimensional human pluripotent stem cells in a novel Vertical\u2010Wheel bioreactor"],"prefix":"10.1002","volume":"3","author":[{"given":"Laureana","family":"Muok","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU\u2010FSU College of Engineering Florida State University  Tallahassee Florida 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State University  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Driscoll","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU\u2010FSU College of Engineering Florida State University  Tallahassee Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunghoon","family":"Jung","sequence":"additional","affiliation":[{"name":"PBS Biotech Inc  Camarillo California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5938-8519","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomedical Engineering, FAMU\u2010FSU College of Engineering Florida State University  Tallahassee Florida 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