{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:13:02Z","timestamp":1789056782375,"version":"build-2803163510"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015M3A9B4066662"],"award-info":[{"award-number":["2015M3A9B4066662"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Controlled Release"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1016\/j.jconrel.2021.06.040","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T03:46:21Z","timestamp":1625197581000},"page":"499-509","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":24,"special_numbering":"C","title":["Intramyocardial delivery of human cardiac stem cell spheroids with enhanced cell engraftment ability and cardiomyogenic potential for myocardial infarct repair"],"prefix":"10.1016","volume":"336","author":[{"given":"Min Ah","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hwa","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Young","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Soo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae Won","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Jin","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Yun","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Tae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Il","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Jin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jconrel.2021.06.040_bb0005","first-page":"E139","article-title":"Heart disease and stroke statistics\u20142020 update: a report from the American Heart Association","author":"Virani","year":"2020","journal-title":"Circulation"},{"issue":"2","key":"10.1016\/j.jconrel.2021.06.040_bb0010","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00109-018-1729-3","article-title":"Approaches to therapeutic angiogenesis for ischemic heart disease","volume":"97","author":"Johnson","year":"2019","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.jconrel.2021.06.040_bb0015","series-title":"Chronic Ischemic Heart Disease Selection of Treatment Modality","author":"Dababneh","year":"2018"},{"issue":"11","key":"10.1016\/j.jconrel.2021.06.040_bb0020","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1161\/CIRCRESAHA.118.313568","article-title":"Medical therapy for heart failure caused by ischemic heart disease","volume":"124","author":"Elgendy","year":"2019","journal-title":"Circ. Res."},{"issue":"10175","key":"10.1016\/j.jconrel.2021.06.040_bb0025","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/S0140-6736(18)31808-7","article-title":"Heart failure drug treatment","volume":"393","author":"Rossignol","year":"2019","journal-title":"Lancet"},{"issue":"9","key":"10.1016\/j.jconrel.2021.06.040_bb0030","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/jocs.13789","article-title":"The current status of stem cell therapy in ischemic heart disease","volume":"33","author":"Michler","year":"2018","journal-title":"J. Card. Surg."},{"issue":"8","key":"10.1016\/j.jconrel.2021.06.040_bb0035","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.3390\/cells9081886","article-title":"The state of art of regenerative therapy in cardiovascular ischemic disease: biology, signaling pathways, and epigenetics of endothelial progenitor cells","volume":"9","author":"Perrotta","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.jconrel.2021.06.040_bb0040","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.addr.2013.12.004","article-title":"Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration","volume":"69","author":"Emmert","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"5","key":"10.1016\/j.jconrel.2021.06.040_bb0045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-020-2542-9","article-title":"The therapeutic potential of mesenchymal stem cells for cardiovascular diseases","volume":"11","author":"Guo","year":"2020","journal-title":"Cell Death Dis."},{"issue":"2","key":"10.1016\/j.jconrel.2021.06.040_bb0050","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3390\/bioengineering5020028","article-title":"Therapeutic use of stem cells for myocardial infarction","volume":"5","author":"Madigan","year":"2018","journal-title":"Bioengineering"},{"issue":"1","key":"10.1016\/j.jconrel.2021.06.040_bb0055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jbm.a.32676","article-title":"Micro and nano-scale in vitro 3D culture system for cardiac stem cells","volume":"94","author":"Hosseinkhani","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"issue":"10","key":"10.1016\/j.jconrel.2021.06.040_bb0060","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nrm2236","article-title":"The third dimension bridges the gap between cell culture and live tissue","volume":"8","author":"Pampaloni","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"6","key":"10.1016\/j.jconrel.2021.06.040_bb0065","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/j.biomaterials.2011.11.049","article-title":"The influence of spheroid formation of human adipose-derived stem cells on chitosan films on stemness and differentiation capabilities","volume":"33","author":"Cheng","year":"2012","journal-title":"Biomaterials"},{"issue":"35","key":"10.1016\/j.jconrel.2021.06.040_bb0070","doi-asserted-by":"crossref","first-page":"8943","DOI":"10.1016\/j.biomaterials.2012.08.069","article-title":"The calcium-dependent regulation of spheroid formation and cardiomyogenic differentiation for MSCs on chitosan membranes","volume":"33","author":"Yeh","year":"2012","journal-title":"Biomaterials"},{"issue":"12","key":"10.1016\/j.jconrel.2021.06.040_bb0075","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3390\/cells8121620","article-title":"Spheroid culture system methods and applications for mesenchymal stem cells","volume":"8","author":"Ryu","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.jconrel.2021.06.040_bb0080","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.biomaterials.2015.01.041","article-title":"A fibrin-supported myocardial organ culture for isolation of cardiac stem cells via the recapitulation of cardiac homeostasis","volume":"48","author":"Kim","year":"2015","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2021.06.040_bb0085","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jconrel.2015.02.013","article-title":"Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction","volume":"205","author":"Chung","year":"2015","journal-title":"J. Control. Release"},{"issue":"03","key":"10.1016\/j.jconrel.2021.06.040_bb0090","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1055\/s-0029-1240758","article-title":"Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia","volume":"58","author":"Hoffmann","year":"2010","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"10.1016\/j.jconrel.2021.06.040_bb0095","article-title":"The use of ex vivo whole-organ imaging and quantitative tissue histology to determine the bio-distribution of fluorescently labeled molecules","volume":"118","author":"McGowan","year":"2016","journal-title":"JoVE"},{"issue":"7","key":"10.1016\/j.jconrel.2021.06.040_bb0100","first-page":"933","article-title":"Quantitative analysis of acute myocardial infarct in rat hearts with ischemia-reperfusion using a high-resolution stationary SPECT system","volume":"43","author":"Liu","year":"2002","journal-title":"J. Nucl. Med."},{"issue":"11","key":"10.1016\/j.jconrel.2021.06.040_bb0105","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1002\/stem.532","article-title":"Cardiospheres recapitulate a niche-like microenvironment rich in stemness and cell-matrix interactions, rationalizing their enhanced functional potency for myocardial repair","volume":"28","author":"Li","year":"2010","journal-title":"Stem Cells"},{"key":"10.1016\/j.jconrel.2021.06.040_bb0110","first-page":"e92","article-title":"Circulation research \u201cIn This Issue\u201d anthology","volume":"122","author":"Williams","year":"2018","journal-title":"Am. Heart Assoc."},{"issue":"4","key":"10.1016\/j.jconrel.2021.06.040_bb0115","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"Assay Drug Develop. Technol."},{"issue":"1","key":"10.1016\/j.jconrel.2021.06.040_bb0120","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"},{"issue":"2","key":"10.1016\/j.jconrel.2021.06.040_bb0125","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1182\/blood-2004-07-2958","article-title":"Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1","volume":"105","author":"Manalo","year":"2005","journal-title":"Blood"},{"issue":"2","key":"10.1016\/j.jconrel.2021.06.040_bb0130","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/1873-3468.12547","article-title":"FGF 11 induced by hypoxia interacts with HIF-1\u03b1 and enhances its stability","volume":"591","author":"Lee","year":"2017","journal-title":"FEBS Lett."},{"issue":"5","key":"10.1016\/j.jconrel.2021.06.040_bb0135","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.3892\/or.2015.4223","article-title":"Hypoxia-induced fibroblast growth factor 11 stimulates capillary-like endothelial tube formation","volume":"34","author":"Yang","year":"2015","journal-title":"Oncol. Rep."},{"issue":"8","key":"10.1016\/j.jconrel.2021.06.040_bb0140","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1182\/blood-2007-08-110338","article-title":"Angiopoietin-1 promotes endothelial cell proliferation and migration through AP-1\u2013dependent autocrine production of interleukin-8","volume":"111","author":"Abdel-Malak","year":"2008","journal-title":"Blood"},{"issue":"8","key":"10.1016\/j.jconrel.2021.06.040_bb0145","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1177\/0300060519857839","article-title":"Cardioprotective effect of IGF-1 against myocardial ischemia\/reperfusion injury through activation of PI3K\/Akt pathway in rats in vivo","volume":"47","author":"Liao","year":"2019","journal-title":"J. Int. Med. Res."},{"issue":"5","key":"10.1016\/j.jconrel.2021.06.040_bb0150","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.4049\/jimmunol.1202996","article-title":"Prostaglandin E2 potentiates mesenchymal stem cell\u2013induced IL-10+ IFN-\u03b3+ CD4+ regulatory T cells to control transplant arteriosclerosis","volume":"190","author":"Hsu","year":"2013","journal-title":"J. Immunol."},{"issue":"6","key":"10.1016\/j.jconrel.2021.06.040_bb0155","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1002\/stem.1695","article-title":"Hhex and Cer1 mediate the Sox17 pathway for cardiac mesoderm formation in embryonic stem cells","volume":"32","author":"Liu","year":"2014","journal-title":"Stem Cells"},{"issue":"3","key":"10.1016\/j.jconrel.2021.06.040_bb0160","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-0442-z","article-title":"Myocardial Bmp2 gain causes ectopic EMT and promotes cardiomyocyte proliferation and immaturity","volume":"9","author":"Prados","year":"2018","journal-title":"Cell Death Dis."},{"issue":"7","key":"10.1016\/j.jconrel.2021.06.040_bb0165","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1258\/ebm.2012.011291","article-title":"Efficient cardiomyogenic differentiation of bone marrow mesenchymal stromal cells by combination of Wnt11 and bone morphogenetic protein 2","volume":"237","author":"Zhang","year":"2012","journal-title":"Exp. Biol. Med."},{"issue":"3","key":"10.1016\/j.jconrel.2021.06.040_bb0170","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0122377","article-title":"Intrapericardial administration of mesenchymal stem cells in a large animal model: a bio-distribution analysis","volume":"10","author":"Bl\u00e1zquez","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.jconrel.2021.06.040_bb0175","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.stem.2009.05.003","article-title":"Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6","volume":"5","author":"Lee","year":"2009","journal-title":"Cell Stem Cell"},{"issue":"3","key":"10.1016\/j.jconrel.2021.06.040_bb0180","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1161\/CIRCHEARTFAILURE.109.931360","article-title":"Microvascular obstruction by intracoronary delivery of mesenchymal stem cells and quantification of resulting myocardial infarction by cardiac magnetic resonance","volume":"3","author":"Grieve","year":"2010","journal-title":"Circ. Heart Fail."},{"issue":"19\u201320","key":"10.1016\/j.jconrel.2021.06.040_bb0185","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1089\/ten.tea.2011.0640","article-title":"Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization","volume":"18","author":"Bhang","year":"2012","journal-title":"Tissue Eng. Part A"},{"issue":"9806","key":"10.1016\/j.jconrel.2021.06.040_bb0190","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/S0140-6736(11)61590-0","article-title":"Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial","volume":"378","author":"Bolli","year":"2011","journal-title":"Lancet"},{"issue":"9","key":"10.1016\/j.jconrel.2021.06.040_bb0195","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1161\/CIRCULATIONAHA.107.734103","article-title":"The myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial: first randomized placebo-controlled study of myoblast transplantation","volume":"117","author":"Menasch\u00e9","year":"2008","journal-title":"Circulation"},{"issue":"3","key":"10.1016\/j.jconrel.2021.06.040_bb0200","doi-asserted-by":"crossref","first-page":"260","DOI":"10.4062\/biomolther.2015.146","article-title":"Long-duration three-dimensional spheroid culture promotes angiogenic activities of adipose-derived mesenchymal stem cells","volume":"24","author":"Lee","year":"2016","journal-title":"Biomol. Ther."},{"issue":"1","key":"10.1016\/j.jconrel.2021.06.040_bb0205","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-19073-4","article-title":"Targeting insulin-like growth factor-I and extracellular matrix interactions in melanoma progression","volume":"8","author":"Murekatete","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jconrel.2021.06.040_bb0210","series-title":"Improving Cell Engraftment in Cardiac Stem Cell Therapy, Stem Cells International 2016","author":"Li","year":"2016"}],"container-title":["Journal of Controlled Release"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365921003382?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365921003382?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T16:04:11Z","timestamp":1759161851000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168365921003382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":42,"alternative-id":["S0168365921003382"],"URL":"https:\/\/doi.org\/10.1016\/j.jconrel.2021.06.040","relation":{},"ISSN":["0168-3659"],"issn-type":[{"value":"0168-3659","type":"print"}],"subject":[],"published":{"date-parts":[[2021,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intramyocardial delivery of human cardiac stem cell spheroids with enhanced cell engraftment ability and cardiomyogenic potential for myocardial infarct repair","name":"articletitle","label":"Article Title"},{"value":"Journal of Controlled Release","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jconrel.2021.06.040","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}