{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:14:19Z","timestamp":1785248059887,"version":"3.55.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council of Singapore","doi-asserted-by":"crossref","award":["CIRG15may018"],"award-info":[{"award-number":["CIRG15may018"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council of Singapore","doi-asserted-by":"crossref","award":["OFIRG16may039"],"award-info":[{"award-number":["OFIRG16may039"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To examine whether transient over-expression of angiopoietin-1 (Ang-1) increases the potency of hiPSC-CMs for treatment of heart failure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Atrial hiPSC-CMs (hiPSC-aCMs) were differentiated from hiPSCs and purified by lactic acid and were transfected with Ang-1 (Ang-1-hiPSC-aCMs) plasmid using lipoSTEM. Ang-1 gene transfection efficiency was characterized in vitro. Gene transfected CMs (1\u00d7106) were seeded into a fibrin\/thrombin patch and implanted on the rat-infarcted left ventricular (LV) anterior wall after myocardial infarction (MI). Echo function was determined at 1- and 6\u00a0weeks post-MI. Immunohistochemistry study was performed at 6\u00a0weeks post-MI. Ang-1 (20 and 40\u2009ng\/mL) protected hiPSC-aCMs from hypoxia through up-regulating pERK1\/2 and inhibiting Bax protein expressions. Ang-1-hiPSC-aCMs transiently secreted Ang-1 protein up to 14\u2009days, with peak level on day-2 post-transfection (24.39\u2009\u00b1\u200913.02\u2009ng\/mL) in vitro. Animal study showed that transplantation of Ang-1-hiPSC-aCM seeded patch more effectively limited rat heart apoptosis at 1\u00a0day post-MI as compared with LipoSTEM-Ang-1 or hiPSC-aCMs transplantation. Ang-1-hiPSC-aCMs transplantation induced host (rat) and donor (human) CM mitosis and arteriole formation, improved cell engraftment rate, more effectively limited LV dilation (EDV\u2009=\u2009460.7\u2009\u00b1\u200996.1\u2009\u03bcL and ESV\u2009=\u2009219.8\u2009\u00b1\u200972.9\u2009\u03bcL) and improved LV global pump function (EF\u2009=\u200953.1\u2009\u00b1\u20099%) as compared with the MI (EDV\u2009=\u2009570.9\u2009\u00b1\u200991.8\u2009\u03bcL, P\u2009=\u20090.033; ESV\u2009=\u2009331.6\u2009\u00b1\u200971.2\u2009\u03bcL, P\u2009=\u20090.011; EF\u2009=\u200942.3\u2009\u00b1\u20094.1%, P\u2009=\u20090.02) or the LipoSTEM-Ang-1 injected (EDV\u2009=\u2009491.4\u2009\u00b1\u2009100.4\u2009\u03bcL, P\u2009=\u20090.854; ESV\u2009=\u2009280.9\u2009\u00b1\u200971.5\u2009\u03bcL, P\u2009=\u20090.287; EF\u2009=\u200943.2\u2009\u00b1\u20094.6, P\u2009=\u20090.039) or hiPSC-CM transplanted (EDV\u2009=\u2009547.9\u2009\u00b1\u200955.5\u2009\u03bcL, P\u2009=\u20090.095; ESV\u2009=\u2009300.2\u2009\u00b1\u200988.4\u2009\u03bcL, P\u2009=\u20090.075; EF\u2009=\u200946\u2009\u00b1\u200910.9%, P\u2009=\u20090.166) animal groups at 6\u00a0weeks post-MI and treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Transient over-expression of Ang-1 enhanced hiPSC-aCM mitosis and engraftment and increased the reparability potency of hiPSC-aCMs for treatment of MI.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa215","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T11:10:14Z","timestamp":1594120214000},"page":"1578-1591","source":"Crossref","is-referenced-by-count":41,"title":["Angiopoietin-1 enhanced myocyte mitosis, engraftment, and the reparability of hiPSC-CMs for treatment of myocardial infarction"],"prefix":"10.1093","volume":"117","author":[{"given":"Zhonghao","family":"Tao","sequence":"first","affiliation":[{"name":"Department of Thoracic and Cardiovascular Surgery, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, 210006 Nanjing, Jiangsu, PR China"},{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore,\u00a05 Hospital Drive, 169609 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szejie","family":"Loo","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore,\u00a05 Hospital Drive, 169609 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Su","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore,\u00a05 Hospital Drive, 169609 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Tan","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore,\u00a05 Hospital Drive, 169609 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhen","family":"Tee","sequence":"additional","affiliation":[{"name":"National Heart Research Institute Singapore, National Heart Centre Singapore,\u00a05 Hospital Drive, 169609 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-0306","authenticated-orcid":false,"given":"Shu Uin","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Surgery, National University of Singapore,\u00a01E Kent Ridge Road, 119228 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical 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