{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T02:26:20Z","timestamp":1774491980905,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":2524,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"name":"Multicentre clinical trial","award":["643478"],"award-info":[{"award-number":["643478"]}]},{"name":"Multicentre clinical trial","award":["643478"],"award-info":[{"award-number":["643478"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Ischaemic heart failure (IHF) patients have a poor prognosis even with current guideline-derived therapy. Intramyocardial injections of autologous or allogeneic mesenchymal stromal cells might improve cardiac function leading to better clinical outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The SCIENCE (Stem Cell therapy in IschEmic Non-treatable Cardiac diseasE) consortium has initiated a Horizon 2020 funded multicentre phase II study in six European countries. It is a double-blind, placebo-controlled trial testing the safety and efficacy of allogeneic Cardiology Stem Cell Centre Adipose-derived Stromal Cells (CSCC_ASC) from healthy donors or placebo in 138 symptomatic IHF patients. Main inclusion criteria are New York Heart Association class II\u2013III, left ventricular ejection fraction &amp;lt;\u200945% and N-terminal pro-B-type natriuretic peptide levels &amp;gt;\u2009300\u2009pg\/mL. Patients are randomized in a 2:1 pattern to receive intramyocardial injections of either CSCC_ASC or placebo. CSCC_ASC and placebo treatments are prepared centralized at Rigshospitalet in 5\u2009mL vials as an off-the-shelf product. Vials are distributed to all clinical partners and stored in nitrogen vapour tanks ready to be used directly after thawing. A total of 100\u2009\u00d7\u2009106 CSCC_ASC or placebo are injected directly into viable myocardium in the infarct border zone using the NOGA XP system (BDS, Cordis, Johnson &amp; Johnson, USA). Primary endpoint is a centralized core-laboratory assessed change in left ventricular end-systolic volume at 6-month follow-up measured by echocardiography. The trial started in January 2017, 58 patients were included and treated until July 2018.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The SCIENCE trial will provide clinical data on efficacy and safety of intramyocardial cell therapy of allogeneic adipose-derived stromal cells from healthy donors in patients with IHF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1412","type":"journal-article","created":{"date-parts":[[2019,2,21]],"date-time":"2019-02-21T01:33:41Z","timestamp":1550712821000},"page":"1032-1041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Rationale and Design of the European Multicentre Study on Stem Cell Therapy in IschEmic Non-Treatable Cardiac diseasE (SCIENCE)"],"prefix":"10.1093","volume":"21","author":[{"given":"Christina","family":"Paitazoglou","sequence":"first","affiliation":[{"name":"Department of Cardiology, Cardiologicum Hamburg , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin W.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiologicum Hamburg , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bojan","family":"Vrtovec","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana , Ljubljana ,","place":["Slovenia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.J.","family":"Chamuleau","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Regenerative Medicine Center, University Medical Center Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bas","family":"van Klarenbosch","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Regenerative Medicine Center, University Medical Center Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojtek","family":"Wojakowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Structural Heart Diseases, Medical University of Silesia , Katowice ,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Michalewska-W\u0142udarczyk","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Structural Heart Diseases, Medical University of Silesia , Katowice ,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariann","family":"Gy\u00f6ngy\u00f6si","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette","family":"Ekblond","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandana","family":"Haack-S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Jaquet","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Asklepios Klinik St. Georg , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Vrangb\u00e6k","sequence":"additional","affiliation":[{"name":"Faculty of Social Sciences and the Faculty of Health Sciences, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Kastrup","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"2026011721313513100_ejhf1412-bib-0001","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1755-1536-1-4","article-title":"Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis","volume":"1","author":"Burchfield","year":"2008","journal-title":"Fibrogenesis Tissue Repair"},{"key":"2026011721313513100_ejhf1412-bib-0002","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1001\/jama.2012.25321","article-title":"Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial","volume":"308","author":"Hare","year":"2012","journal-title":"JAMA"},{"key":"2026011721313513100_ejhf1412-bib-0003","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1161\/CIRCRESAHA.115.306332","article-title":"A phase II dose-escalation study of allogeneic mesenchymal precursor cells in patients with ischemic or nonischemic heart failure","volume":"117","author":"Perin","year":"2015","journal-title":"Circ Res"},{"key":"2026011721313513100_ejhf1412-bib-0004","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1093\/eurheartj\/ehv136","article-title":"Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial)","volume":"36","author":"Mathiasen","year":"2015","journal-title":"Eur Heart J"},{"key":"2026011721313513100_ejhf1412-bib-0005","doi-asserted-by":"crossref","first-page":"805","DOI":"10.4244\/EIJV7I7A127","article-title":"Transendocardial autologous bone marrow in myocardial infarction induced heart failure, two-year follow-up in an open-label phase I safety study (the TABMMI study)","volume":"7","author":"de la Fuente","year":"2011","journal-title":"EuroIntervention"},{"key":"2026011721313513100_ejhf1412-bib-0006","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/s13287-018-0969-z","article-title":"Linking cell function with perfusion: insights from the transcatheter delivery of bone marrow-derived CD133(+) cells in ischemic refractory cardiomyopathy trial (RECARDIO)","volume":"9","author":"Bassetti","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"2026011721313513100_ejhf1412-bib-0007","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1478-811X-9-12","article-title":"Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC","volume":"9","author":"Hass","year":"2011","journal-title":"Cell Commun Signal"},{"key":"2026011721313513100_ejhf1412-bib-0008","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1182\/blood-2007-02-074997","article-title":"Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2","volume":"111","author":"Spaggiari","year":"2008","journal-title":"Blood"},{"key":"2026011721313513100_ejhf1412-bib-0009","doi-asserted-by":"crossref","first-page":"455","DOI":"10.5966\/sctm.2012-0184","article-title":"Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts","volume":"2","author":"Melief","year":"2013","journal-title":"Stem Cells Transl Med"},{"key":"2026011721313513100_ejhf1412-bib-0010","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1089\/ten.2006.0165","article-title":"Stem cells from adipose tissue allow challenging new concepts for regenerative medicine","volume":"13","author":"Helder","year":"2007","journal-title":"Tissue Eng"},{"key":"2026011721313513100_ejhf1412-bib-0011","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3727\/096368907783338190","article-title":"Adipose-derived cells","volume":"16","author":"Meliga","year":"2007","journal-title":"Cell Transplant"},{"key":"2026011721313513100_ejhf1412-bib-0012","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1159\/000110447","article-title":"Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia","volume":"20","author":"Kim","year":"2007","journal-title":"Cell Physiol Biochem"},{"key":"2026011721313513100_ejhf1412-bib-0013","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/sctm.17-0040","article-title":"Cryopreserved off-the-shelf allogeneic adipose-derived stromal cells for therapy in patients with ischemic heart disease and heart failure \u2013 a safety study","volume":"6","author":"Kastrup","year":"2017","journal-title":"Stem Cells Transl Med"},{"key":"2026011721313513100_ejhf1412-bib-0014","first-page":"1","article-title":"Development of large-scale manufacturing of adipose-derived stromal cells for clinical applications using bioreactors and human platelet lysate","volume":"17","author":"Haack-Sorensen","year":"2018","journal-title":"Scand J Clin Lab Invest"},{"key":"2026011721313513100_ejhf1412-bib-0015","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s12967-016-1080-9","article-title":"Culture expansion of adipose derived stromal cells. A closed automated Quantum Cell Expansion System compared with manual flask-based culture","volume":"14","author":"Haack-Sorensen","year":"2016","journal-title":"J Transl Med"},{"key":"2026011721313513100_ejhf1412-bib-0016","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.jcyt.2013.02.006","article-title":"Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal\/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT)","volume":"15","author":"Bourin","year":"2013","journal-title":"Cytotherapy"},{"key":"2026011721313513100_ejhf1412-bib-0017","doi-asserted-by":"crossref","first-page":"732","DOI":"10.4244\/EIJV8I6A113","article-title":"Percutaneous, transendocardial injection of bone marrow-derived mononuclear cells in heart failure patients following acute ST-elevation myocardial infarction: ALSTER-Stem Cell trial","volume":"8","author":"Heeger","year":"2012","journal-title":"EuroIntervention"},{"key":"2026011721313513100_ejhf1412-bib-0018","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/5237063","article-title":"Adipose-derived stromal cells for treatment of patients with chronic ischemic heart disease (MyStromalCell trial): a randomized placebo-controlled study","volume":"2017","author":"Qayyum","year":"2017","journal-title":"Stem Cells Int"},{"key":"2026011721313513100_ejhf1412-bib-0019","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/nrcardio.2011.64","article-title":"Diagnostic and prognostic value of 3D NOGA mapping in ischemic heart disease","volume":"8","author":"Gyongyosi","year":"2011","journal-title":"Nat Rev Cardiol"},{"key":"2026011721313513100_ejhf1412-bib-0020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0113245","article-title":"Comparison of NOGA endocardial mapping and cardiac magnetic resonance imaging for determining infarct size and infarct transmurality for intramyocardial injection therapy using experimental data","volume":"9","author":"Pavo","year":"2014","journal-title":"PLoS One"},{"key":"2026011721313513100_ejhf1412-bib-0021","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s10554-016-0852-x","article-title":"Three dimensional fusion of electromechanical mapping and magnetic resonance imaging for real-time navigation of intramyocardial cell injections in a porcine model of chronic myocardial infarction","volume":"32","author":"van Slochteren","year":"2016","journal-title":"Int J Cardiovasc Imaging"},{"key":"2026011721313513100_ejhf1412-bib-0022","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1161\/01.CIR.76.1.44","article-title":"Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction","volume":"76","author":"White","year":"1987","journal-title":"Circulation"},{"key":"2026011721313513100_ejhf1412-bib-0023","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.echo.2008.11.005","article-title":"Prognostic value of left ventricular end-systolic volume index as a predictor of heart failure hospitalization in stable coronary artery disease: data from the Heart and Soul Study","volume":"22","author":"McManus","year":"2009","journal-title":"J Am Soc Echocardiogr"},{"key":"2026011721313513100_ejhf1412-bib-0024","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1161\/CIRCRESAHA.116.304346","article-title":"Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data","volume":"116","author":"Gyongyosi","year":"2015","journal-title":"Circ Res"},{"key":"2026011721313513100_ejhf1412-bib-0025","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1016\/S0140-6736(16)30138-6","article-title":"IxCELL-DCM: rejuvenation for cardiac regenerative therapy?","volume":"387","author":"Povsic","year":"2016","journal-title":"Lancet"},{"key":"2026011721313513100_ejhf1412-bib-0026","first-page":"169","article-title":"The Athena trials: autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction","volume":"89","author":"Henry","year":"2017","journal-title":"Catheter Cardiovasc Interv"},{"key":"2026011721313513100_ejhf1412-bib-0027","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.ahj.2011.01.028","article-title":"A randomized study of transendocardial injection of autologous bone marrow mononuclear cells and cell function analysis in ischemic heart failure (FOCUS-HF)","volume":"161","author":"Perin","year":"2011","journal-title":"Am Heart J"},{"key":"2026011721313513100_ejhf1412-bib-0028","first-page":"648","article-title":"Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial","volume":"38","author":"Bartunek","year":"2017","journal-title":"Eur Heart J"},{"key":"2026011721313513100_ejhf1412-bib-0029","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1161\/CIRCRESAHA.117.311827","article-title":"Dose comparison study of allogeneic mesenchymal stem cells in patients with ischemic cardiomyopathy (the TRIDENT study)","volume":"121","author":"Florea","year":"2017","journal-title":"Circ Res"},{"key":"2026011721313513100_ejhf1412-bib-0030","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/8506370","article-title":"Rationale and design of the first double-blind, placebo-controlled trial with allogeneic adipose tissue-derived stromal cell therapy in patients with ischemic heart failure: a phase II Danish multicentre study","volume":"2017","author":"Kastrup","year":"2017","journal-title":"Stem Cells Int"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.1412","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.1412","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.1412","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/8\/1032\/66192772\/eurjhf_21_8_1032.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/21\/8\/1032\/66192772\/eurjhf_21_8_1032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:32:10Z","timestamp":1768703530000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/21\/8\/1032\/8407997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,20]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,2,20]]},"published-print":{"date-parts":[[2019,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.1412","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,8]]},"published":{"date-parts":[[2019,2,20]]},"assertion":[{"value":"2018-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}