{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:18:42Z","timestamp":1790180322482,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":1039,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>The study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II\u2013III, left ventricular ejection fraction (LVEF) &amp;lt;45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels &amp;gt;300\u2009pg\/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3\u2009\u00b1\u20095.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (\u22122.0\u2009\u00b1\u20096.0 ml, p = 0.736) and LVEF (\u22121.6\u2009\u00b1\u20091.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2772","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:30:07Z","timestamp":1673839807000},"page":"576-587","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Effect of Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cell Treatment in Chronic Ischaemic Heart Failure with Reduced Ejection Fraction \u2013 the SCIENCE Trial"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-0002","authenticated-orcid":false,"given":"Abbas Ali","family":"Qayyum","sequence":"first","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Frljak","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana , Ljubljana ,","place":["Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andraz","family":"Cerar","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana , Ljubljana ,","place":["Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Poglajen","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana , Ljubljana ,","place":["Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Traxler-Weidenauer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Nadrowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Structural Heart Diseases, Medical University of Silesia , Katowice ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Paitazoglou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Asklepios Klinik St. Georg , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojan","family":"Vrtovec","sequence":"additional","affiliation":[{"name":"Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana , Ljubljana ,","place":["Slovenia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin W.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Asklepios Klinik St. Georg , Hamburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojtek","family":"Wojakowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Structural Heart Diseases, Medical University of Silesia , Katowice ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariann","family":"Gy\u00f6ngy\u00f6si","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan","family":"Kraaijeveld","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Regenerative Medicine Center, University Medical Center Utrecht , Utrecht ,","place":["The 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and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Richard","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M\u00f8nsted","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjarke","family":"Follin","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen , Copenhagen 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