{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T16:23:39Z","timestamp":1769185419468,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,7,24]],"date-time":"2015-07-24T00:00:00Z","timestamp":1437696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia, Portugal","award":["PTDC\/EQU-EQU\/114231\/2009"],"award-info":[{"award-number":["PTDC\/EQU-EQU\/114231\/2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human mesenchymal stem\/stromal cells (MSC) are promising candidates for cell\u2010based therapies and the development of microcarrier\u2010based cultures in scalable bioreactors with well\u2010defined xenogeneic\u2010free components represent important milestones towards the clinical\u2010scale production of these cells. In this work, we optimized our previously developed xeno\u2010free microcarrier\u2010based system for the scalable expansion of human MSC isolated from bone marrow (BM MSC) and adipose\u2010derived stem\/stromal cells (ASC). By adapting the agitation\/feeding protocol at the initial cell seeding\/cultivation stage in spinner flasks, we were able to maximize cell expansion rate and final cell yield. Maximal cell densities of 3.6 \u00d7 10<jats:sup>5<\/jats:sup> and 1.9 \u00d7 10<jats:sup>5<\/jats:sup> cells\/mL were obtained for BM MSC (0.60 \u00b1 0.04 day<jats:sup>\u20131<\/jats:sup>) and ASC (0.9 \u00b1 0.1 day<jats:sup>\u20131<\/jats:sup>) cultures, upon seven and eight days of cultivation, respectively. Ready\u2010to\u2010use microcarriers Synthemax\u00ae II and Enhanced Attachment\u00ae supported identical expansion performance of BM MSC, turning those effective alternatives to the pre\u2010coated plastic microcarriers used in our xeno\u2010free scalable culture system. Importantly, expanded MSC maintained their immunophenotype and multilineage differentiation potential. Moreover, secretome analysis suggested a priming effect of stirred culture conditions on cytokine production by MSC. This culture system yielded considerable final cell densities that can be scaled\u2010up to controlled large\u2010scale bioreactors allowing a more efficient, safe and cost\u2010effective MSC production for clinical settings.<\/jats:p>","DOI":"10.1002\/biot.201400586","type":"journal-article","created":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T06:06:59Z","timestamp":1435817219000},"page":"1235-1247","source":"Crossref","is-referenced-by-count":64,"title":["A xeno\u2010free microcarrier\u2010based stirred culture system for the scalable expansion of human mesenchymal stem\/stromal cells isolated from bone marrow and adipose tissue"],"prefix":"10.1002","volume":"10","author":[{"given":"Joana G.","family":"Carmelo","sequence":"first","affiliation":[]},{"given":"Ana","family":"Fernandes\u2010Platzgummer","sequence":"additional","affiliation":[]},{"given":"Maria Margarida","family":"Diogo","sequence":"additional","affiliation":[]},{"given":"Cl\u00e1udia Lobato","family":"da Silva","sequence":"additional","affiliation":[]},{"given":"Joaquim M. 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