{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:12:54Z","timestamp":1793301174249,"version":"4.5.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"15","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["RM\/17\/1\/33377"],"award-info":[{"award-number":["RM\/17\/1\/33377"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["FS\/15\/33\/31608"],"award-info":[{"award-number":["FS\/15\/33\/31608"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council","award":["MR\/R026416\/1"],"award-info":[{"award-number":["MR\/R026416\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,9]]},"abstract":"<jats:p>\n                    Engineered heart tissue (EHT) strategies, by combining cells within a hydrogel matrix, may be a novel therapy for heart failure. EHTs restore cardiac function in rodent injury models, but more data are needed in clinically relevant settings. Accordingly, an upscaled EHT patch (2.5 cm\n                    <jats:italic>\u00d7<\/jats:italic>\n                    1.5 cm\n                    <jats:italic>\u00d7<\/jats:italic>\n                    1.5 mm) consisting of up to 20 million human induced pluripotent stem cell\u2013derived cardiomyocytes (hPSC-CMs) embedded in a fibrin-based hydrogel was developed. A rabbit myocardial infarction model was then established to test for feasibility and efficacy. Our data showed that hPSC-CMs in EHTs became more aligned over 28 days and had improved contraction kinetics and faster calcium transients. Blinded echocardiographic analysis revealed a significant improvement in function in infarcted hearts that received EHTs, along with reduction in infarct scar size by 35%. Vascularization from the host to the patch was observed at week 1 and stable to week 4, but electrical coupling between patch and host heart was not observed. In vivo telemetry recordings and ex vivo arrhythmia provocation protocols showed that the patch was not pro-arrhythmic. In summary, EHTs improved function and reduced scar size without causing arrhythmia, which may be due to the lack of electrical coupling between patch and host heart.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.144068","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T16:40:43Z","timestamp":1628613643000},"source":"Crossref","is-referenced-by-count":62,"title":["In vivo grafting of large engineered heart tissue patches for cardiac repair"],"prefix":"10.1172","volume":"6","author":[{"given":"Richard J.","family":"Jabbour","sequence":"first","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-7453","authenticated-orcid":true,"given":"Thomas J.","family":"Owen","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7567-3387","authenticated-orcid":true,"given":"Pragati","family":"Pandey","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1054-6456","authenticated-orcid":true,"given":"Marina","family":"Reinsch","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, Hamburg University, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Wang","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ois\u00edn","family":"King","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam Steven","family":"Couch","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafni","family":"Pantou","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Pitcher","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-1014","authenticated-orcid":true,"given":"Rasheda A.","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-9046","authenticated-orcid":true,"given":"Fotios G.","family":"Pitoulis","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balvinder S.","family":"Handa","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worrapong","family":"Kit-Anan","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Perbellini","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4670-361X","authenticated-orcid":true,"given":"Rachel C.","family":"Myles","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, University of Glasgow, Glasgow, Scotland, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8888-627X","authenticated-orcid":true,"given":"Daniel J.","family":"Stuckey","sequence":"additional","affiliation":[{"name":"Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dunne","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, University of Glasgow, Glasgow, Scotland, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8036-6253","authenticated-orcid":true,"given":"Mayooran","family":"Shanmuganathan","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-8078","authenticated-orcid":true,"given":"Nicholas S.","family":"Peters","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-4368","authenticated-orcid":true,"given":"Fu Siong","family":"Ng","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-0517","authenticated-orcid":true,"given":"Florian","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, Hamburg University, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2761-0696","authenticated-orcid":true,"given":"Cesare M.","family":"Terracciano","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4821-9741","authenticated-orcid":true,"given":"Godfrey L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, University of Glasgow, Glasgow, Scotland, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1750-1170","authenticated-orcid":true,"given":"Thomas","family":"Eschenhagen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Science, Hamburg University, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3651-6354","authenticated-orcid":true,"given":"Sian E.","family":"Harding","sequence":"additional","affiliation":[{"name":"National Heart & Lung Institute, Imperial College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61728-0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304386"},{"issue":"3 pt b","key":"B3","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.scr.2014.06.005","article-title":"Cardiac regeneration using pluripotent stem cells\u2014progression to large animal models","volume":"13","author":"Chong","year":"2014","journal-title":"Stem Cell Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310738"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024145"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nm1394"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf8781"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature13233"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.04.005"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.2007.00858.x"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.10.007"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199704)247:4<521::AID-AR11>3.0.CO;2-R"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.113.000334"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01946-x"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.09.024"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030785"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.047904"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2009.02.001"},{"issue":"6 pt 2","key":"B19","first-page":"H1710","article-title":"Force-frequency relations and response to ryanodine in failing rabbit hearts","volume":"263","author":"Ezzaher","year":"1992","journal-title":"Am J Physiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.11.019"},{"issue":"3 pt 2","key":"B21","first-page":"H634","article-title":"Left ventricular function and beta-adrenoceptors in rabbit failing heart","volume":"258","author":"Gilson","year":"1990","journal-title":"Am J Physiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/21.10.737"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.08.006"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s13028-014-0054-2"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092020203"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46409-z"},{"issue":"suppl 4","key":"B27","doi-asserted-by":"crossref","first-page":"iv85","DOI":"10.1093\/europace\/euw354","article-title":"Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart","volume":"18","author":"Quinn","year":"2016","journal-title":"Europace"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200250109"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.033"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1327"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)90440-5"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00404.2012"},{"issue":"3","key":"B33","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1161\/CIRCRESAHA.117.312067","article-title":"MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo","volume":"122","author":"Sala","year":"2018","journal-title":"Circ Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121264"},{"issue":"4","key":"B35","first-page":"454","article-title":"Echocardiographic evaluation of cardiac structure and function during exercise training in the developing Sprague-Dawley rat","volume":"50","author":"Hayward","year":"2011","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)75765-7"},{"issue":"11","key":"B37","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1161\/01.RES.0000149531.02904.09","article-title":"Alterations in myofilament function contribute to left ventricular dysfunction in pigs early after myocardial infarction","volume":"95","author":"van der Velden","year":"2004","journal-title":"Circ Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.110.962282"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvc.2014.03.004"},{"issue":"4","key":"B40","first-page":"361","article-title":"Echocardiographic parameters of clinically normal geriatric rhesus macaques (macaca mulatta)","volume":"56","author":"Ueda","year":"2017","journal-title":"J Am Assoc Lab Anim Sci"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/144068\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:46:03Z","timestamp":1779147963000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/144068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,9]]},"references-count":40,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8,9]]},"published-print":{"date-parts":[[2021,8,9]]}},"alternative-id":["10.1172\/jci.insight.144068"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.144068","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,9]]},"article-number":"e144068"}}