{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:55:01Z","timestamp":1792677301594,"version":"4.5.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2018,1,5]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The effectiveness of transplanted, human induced pluripotent stem cell\u2013derived cardiomyocytes (hiPSC-CMs) for treatment of ischemic myocardial injury is limited by the exceptionally low engraftment rate.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To determine whether overexpression of the cell cycle activator CCND2 (cyclin D2) in hiPSC-CMs can increase the graft size and improve myocardial recovery in a mouse model of myocardial infarction by increasing the proliferation of grafted cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Human CCND2 was delivered to hiPSCs via lentiviral-mediated gene transfection. In cultured cells, markers for cell cycle activation and proliferation were \u22483- to 7-folds higher in CCND2-overexpressing hiPSC-CMs (hiPSC-CCND2\n              <jats:sup>OE<\/jats:sup>\n              CMs) than in hiPSC-CMs with normal levels of CCND2 (hiPSC-CCND2\n              <jats:sup>WT<\/jats:sup>\n              CMs;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). The pluripotent genes (Oct 4, Sox2, and Nanog) decrease to minimal levels and undetectable levels at day 1 and 10 after differentiating to CMs. In the mouse myocardial infarction model, cardiac function, infarct size, and the number of engrafted cells were similar at week 1 after treatment with hiPSC-CCND2\n              <jats:sup>OE<\/jats:sup>\n              CMs or hiPSC-CCND2\n              <jats:sup>WT<\/jats:sup>\n              CMs but was about tripled in hiPSC-CCND2\n              <jats:sup>OE<\/jats:sup>\n              CM\u2013treated than in hiPSC-CCND2\n              <jats:sup>WT<\/jats:sup>\n              CM\u2013treated animals at week 4 (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). The cardiac function and infarct size were significantly better in both cell treatment groups\u2019 hearts than in control hearts, which was most prominent in hiPSC-CCND2\n              <jats:sup>OE<\/jats:sup>\n              CM\u2013treated animals (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05, each). No tumor formation was observed in any hearts.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>CCND2 overexpression activates cell cycle progression in hiPSC-CMs that results in a significant enhanced potency for myocardial repair as evidenced by remuscularization of injured myocardium. This left ventricular muscle regeneration and increased angiogenesis in border zone are accompanied by a significant improvement of left ventricular chamber function.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.117.311504","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T00:11:41Z","timestamp":1507680701000},"page":"88-96","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":153,"title":["CCND2 Overexpression Enhances the Regenerative Potency of Human Induced Pluripotent Stem Cell\u2013Derived Cardiomyocytes"],"prefix":"10.1161","volume":"122","author":[{"given":"Wuqiang","family":"Zhu","sequence":"first","affiliation":[{"name":"From the Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (W.Z., M.Z., S.M., J.Z.); and Department of Physiology and Pathophysiology, Fudan University, Shanghai, China (M.Z., S.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhao","sequence":"additional","affiliation":[{"name":"From the Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (W.Z., M.Z., S.M., J.Z.); and Department of Physiology and Pathophysiology, Fudan University, Shanghai, China (M.Z., S.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saidulu","family":"Mattapally","sequence":"additional","affiliation":[{"name":"From the Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (W.Z., M.Z., S.M., J.Z.); and Department of Physiology and Pathophysiology, Fudan University, Shanghai, China (M.Z., S.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (W.Z., M.Z., S.M., J.Z.); and Department of Physiology and Pathophysiology, Fudan University, Shanghai, China (M.Z., S.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (W.Z., M.Z., S.M., J.Z.); and Department of Physiology and Pathophysiology, Fudan University, Shanghai, China (M.Z., S.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-009-9408-3"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.36"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10147"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2015"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300219"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.02.014"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.11.009"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.015231"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11139"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11044"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.176115"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8140423"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0898-929"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.659730"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.12.036"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.03.009"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000152326.91223.4F"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr302"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm101"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.000641"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001317"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3791\/55142"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.310277"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.100"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0168"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.10.029"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00559.2015"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15372"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1306705"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.060"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.026"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0163"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191169098"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00510-2"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1302.013"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0405-367"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm912"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.192237"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19111"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04542"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.117.311504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T05:15:36Z","timestamp":1715577336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.117.311504"}},"subtitle":["Remuscularization of Injured Ventricle"],"short-title":[],"issued":{"date-parts":[[2018,1,5]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1,5]]}},"alternative-id":["10.1161\/CIRCRESAHA.117.311504"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.117.311504","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,5]]},"assertion":[{"value":"2017-10-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}