{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:27:34Z","timestamp":1771028854266,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T00:00:00Z","timestamp":1465776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2012\/23228\u20104; 2013\/23599\u20105"],"award-info":[{"award-number":["2012\/23228\u20104; 2013\/23599\u20105"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["FAPESP 2013\/08135\u20102, CNPq 573754\u20102008\u20100 and FAPESP 2008\/578773"],"award-info":[{"award-number":["FAPESP 2013\/08135\u20102, CNPq 573754\u20102008\u20100 and FAPESP 2008\/578773"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/BIO\/04565\/2013;PTDC\/EQU-EQU\/114231\/2009"],"award-info":[{"award-number":["UID\/BIO\/04565\/2013;PTDC\/EQU-EQU\/114231\/2009"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["HMSP\u2010ICT\/0001\/2011; SFRH\/BPD\/82062\/2011"],"award-info":[{"award-number":["HMSP\u2010ICT\/0001\/2011; SFRH\/BPD\/82062\/2011"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mesenchymal stem\/stromal cells (MSC) are being widely explored as promising candidates for cell\u2010based therapies. Among the different human MSC origins exploited, umbilical cord represents an attractive and readily available source of MSC that involves a non\u2010invasive collection procedure. In order to achieve relevant cell numbers of human MSC for clinical applications, it is crucial to develop scalable culture systems that allow bioprocess control and monitoring, combined with the use of serum\/xenogeneic (xeno)\u2010free culture media. In the present study, we firstly established a spinner flask culture system combining gelatin\u2010based Cultispher<jats:sup>\u00ae<\/jats:sup>S microcarriers and xeno\u2010free culture medium for the expansion of umbilical cord matrix (UCM)\u2010derived MSC. This system enabled the production of 2.4 (\u00b11.1) x10<jats:sup>5<\/jats:sup> cells\/mL (<jats:italic>n<\/jats:italic> = 4) after 5 days of culture, corresponding to a 5.3 (\u00b11.6)\u2010fold increase in cell number. The established protocol was then implemented in a stirred\u2010tank bioreactor (800 mL working volume) (<jats:italic>n<\/jats:italic> = 3) yielding 115 million cells after 4 days. Upon expansion under stirred conditions, cells retained their differentiation ability and immunomodulatory potential. The development of a scalable microcarrier\u2010based stirred culture system, using xeno\u2010free culture medium that suits the intrinsic features of UCM\u2010derived MSC represents an important step towards a GMP compliant large\u2010scale production platform for these promising cell therapy candidates.<\/jats:p>","DOI":"10.1002\/biot.201500532","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T13:08:56Z","timestamp":1462972136000},"page":"1048-1059","source":"Crossref","is-referenced-by-count":65,"title":["Stirred tank bioreactor culture combined with serum\u2010\/xenogeneic\u2010free culture medium enables an efficient expansion of umbilical cord\u2010derived mesenchymal stem\/stromal cells"],"prefix":"10.1002","volume":"11","author":[{"given":"Amanda","family":"Mizukami","sequence":"first","affiliation":[{"name":"Hemotherapy Center of Ribeir\u00e3o Preto, Faculty of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto\u2010SP Brazil"}]},{"given":"Ana","family":"Fernandes\u2010Platzgummer","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisboa Portugal"}]},{"given":"Joana G.","family":"Carmelo","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisboa Portugal"}]},{"given":"Kamilla","family":"Swiech","sequence":"additional","affiliation":[{"name":"Hemotherapy Center of Ribeir\u00e3o Preto, Faculty of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto\u2010SP Brazil"},{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto\u2010SP Brazil"}]},{"given":"Dimas T.","family":"Covas","sequence":"additional","affiliation":[{"name":"Hemotherapy Center of Ribeir\u00e3o Preto, Faculty of Medicine of Ribeir\u00e3o Preto University of S\u00e3o Paulo  Ribeir\u00e3o Preto\u2010SP Brazil"}]},{"given":"Joaquim M. S.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisboa Portugal"}]},{"given":"Cl\u00e1udia L.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and IBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico Universidade de Lisboa  Lisboa Portugal"}]}],"member":"311","published-online":{"date-parts":[[2016,6,13]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"193519","article-title":"Translating research into clinical scale manufacturing of mesenchymal stromal cells","volume":"2010","author":"Bieback K.","year":"2011","journal-title":"Stem Cells Int."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-060-7_18"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-009-0377-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1089\/107632701300062859","article-title":"Multilineage cells from human adipose tissue: Implications for cell\u2010based therapies","volume":"7","author":"Zuk P. A.","year":"2011","journal-title":"Tissue Eng."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0594"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-014-2714-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v6.i2.195"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201200340"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.09.008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.03.034"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6215-12-62"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-011-0116-z"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60690-X"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1886"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.2012.00836.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25187"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.02.015"},{"key":"e_1_2_7_19_1","first-page":"28","article-title":"Scale\u2010up of human mesenchymal stem cells on microcarriers in suspension in a single\u2010use bioreactor","volume":"25","author":"Kehoe D.","year":"2012","journal-title":"BioPharm Int."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-013-1211-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24425"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2013.05.024"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.11.001"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2014.01.417"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt117"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2011.06.009"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2014.0299"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/026119290203000208"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1783-7"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0066-5"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt477"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2013.11.004"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.02.012"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11446"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085040"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400586"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2011.0255"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2013.10.010"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25281"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0031-3"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2007.05.031"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21987"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-002-0462-7"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.patbio.2008.06.004"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2000.4761"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1707"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-011-0695-4"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260290117"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.658"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.5772\/59385"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2013.0664"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt217"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368910X532756"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2012.10.012"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2008.0345"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.73"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1527"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/cite.201200180"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105602"},{"key":"e_1_2_7_61_1","first-page":"10","article-title":"Isolation and partial characterization of human amniotic epithelial cells: The effect of trypsin","volume":"6","author":"Tabatabaei M.","year":"2014","journal-title":"Avicenna J. Med. Biotechnol."},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/698076"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.08.002"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.05.001"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbiot.201500532","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.201500532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T17:41:37Z","timestamp":1759945297000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.201500532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,13]]},"references-count":63,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1002\/biot.201500532"],"URL":"https:\/\/doi.org\/10.1002\/biot.201500532","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,13]]}}}