{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:59:43Z","timestamp":1770418783429,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Operational Programme of Lisbon","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Regional Operational Programme of Lisbon","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}]},{"name":"Regional Operational Programme of Lisbon","award":["SFRH\/BD\/78774\/2011"],"award-info":[{"award-number":["SFRH\/BD\/78774\/2011"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["SFRH\/BD\/78774\/2011"],"award-info":[{"award-number":["SFRH\/BD\/78774\/2011"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Portuguese Platform of BioImaging","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Portuguese Platform of BioImaging","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}]},{"name":"Portuguese Platform of BioImaging","award":["SFRH\/BD\/78774\/2011"],"award-info":[{"award-number":["SFRH\/BD\/78774\/2011"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy","award":["SFRH\/BD\/78774\/2011"],"award-info":[{"award-number":["SFRH\/BD\/78774\/2011"]}]},{"DOI":"10.13039\/501100015620","name":"Institute for Bioengineering and Biosciences","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100015620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015620","name":"Institute for Bioengineering and Biosciences","doi-asserted-by":"publisher","award":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}],"id":[{"id":"10.13039\/501100015620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015620","name":"Institute for Bioengineering and Biosciences","doi-asserted-by":"publisher","award":["SFRH\/BD\/78774\/2011"],"award-info":[{"award-number":["SFRH\/BD\/78774\/2011"]}],"id":[{"id":"10.13039\/501100015620","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":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"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":["UIDB\/04565\/2020"],"award-info":[{"award-number":["UIDB\/04565\/2020"]}],"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":["SFRH\/BD\/78774\/2011"],"award-info":[{"award-number":["SFRH\/BD\/78774\/2011"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2022,11,23]]},"abstract":"<jats:p>Human induced pluripotent stem cells (hiPSCs) can be efficiently differentiated into cardiomyocytes (CMs), which can be used for cardiac disease modeling, for drug screening, and to regenerate damaged myocardium. Implementation of xeno-free culture systems is essential to fully explore the potential of these cells. However, differentiation using xeno-free adhesion matrices often results in low CM yields and lack of functional CM sheets, capable of enduring additional maturation stages. Here, we established a xeno-free CM differentiation platform using TeSR\/Synthemax, including a replating step and integrated with two versatile purification\/enrichment metabolic approaches. Results showed that the replating step was essential to reestablish a fully integrated, closely-knit CM sheet. In addition, replating contributed to increase the cTnT expression from 65% to 75% and the output from 2.2 to 3.1 CM per hiPSC, comparable with the efficiency observed when using TeSR\/Matrigel. In addition, supplementation with PluriSin1 and Glu-Lac+ medium allowed increasing the CM content over 80% without compromising CM sheet integrity or functionality. Thus, this xeno-free differentiation platform is a reliable and robust method to produce hiPSC-derived CMs, increasing the possibility of using these cells safely for a wide range of applications.<\/jats:p>","DOI":"10.1155\/2022\/4542719","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T19:36:58Z","timestamp":1669318618000},"page":"1-11","source":"Crossref","is-referenced-by-count":3,"title":["Xeno-Free Integrated Platform for Robust Production of Cardiomyocyte Sheets from hiPSCs"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9133-8856","authenticated-orcid":true,"given":"Tiago P.","family":"Dias","sequence":"first","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-5037","authenticated-orcid":true,"given":"T\u00e2nia","family":"Baltazar","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3205-9459","authenticated-orcid":true,"given":"Sandra N.","family":"Pinto","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4651-2832","authenticated-orcid":true,"given":"Tiago G.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-265X","authenticated-orcid":true,"given":"F\u00e1bio","family":"Fernandes","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-4455","authenticated-orcid":true,"given":"Maria Margarida","family":"Diogo","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-6598","authenticated-orcid":true,"given":"Manuel","family":"Prieto","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2405-5845","authenticated-orcid":true,"given":"Joaquim M. S.","family":"Cabral","sequence":"additional","affiliation":[{"name":"iBB\u2014Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy at Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal"}]}],"member":"311","reference":[{"key":"1","article-title":"Cardiovascular diseases (Fact sheet)","author":"World Health Organization","year":"2021"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/433585a"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164680"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.026"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/10_2019_117"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.05.011"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.08.002"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.05.016"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.11.047"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024145"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-010-9297-z"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2011.08.005"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151264"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1593"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1629"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2231"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2008-0291"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2999"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0586"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.03.198"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2005"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50899-2"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0137"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.04.005"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-013-9482-z"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023657"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.11.015"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.09.013"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.150"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.03.023"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3271"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.050"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1327"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering6030071"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0563"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45047-9"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13602"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1038\/srep29933"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033283"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-30936-2"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08713-4"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2021.01.018"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-87186-y"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw200"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw235"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045963"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-013-9510-z"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10312"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.111.973420"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2524"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0016-3"}],"container-title":["Stem Cells International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2022\/4542719.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2022\/4542719.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/sci\/2022\/4542719.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T19:37:07Z","timestamp":1669318627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/sci\/2022\/4542719\/"}},"subtitle":[],"editor":[{"given":"Ren-Ke","family":"Li","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,11,23]]},"references-count":52,"alternative-id":["4542719","4542719"],"URL":"https:\/\/doi.org\/10.1155\/2022\/4542719","relation":{},"ISSN":["1687-9678","1687-966X"],"issn-type":[{"value":"1687-9678","type":"electronic"},{"value":"1687-966X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11,23]]}}}