{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:40:27Z","timestamp":1787888427658,"version":"build-2784847793"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515012484"],"award-info":[{"award-number":["2021A1515012484"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Myocardial infarction (MI) is the most predominant type of cardiovascular diseases with high mortality and morbidity. Stem cell therapy, especially cardiac progenitor cell therapy, has been proposed as a promising approach for cardiac regeneration and MI treatment. Previously, we have successfully generated cardiac progenitor\u2010like cells, induced cardiosphere (iCS), via somatic reprogramming. However, the genome integration characteristic of virus\u2010based reprogramming approach hampered their therapeutic applications due to the risk of tumour formation. In the current study, we aim to establish a safer iCS generation strategy with transgene\u2010free approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Four transgene\u2010free approaches for somatic reprogramming, including episome, minicircle, self\u2010replicative RNA, and sendai virus, were compared, from the perspective of cardiac progenitor marker expression, iCS formation, and cardiac differentiation. The therapeutic effects were assessed in the mouse model of MI, from the perspective of survival rate, cardiac function, and structural alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The self\u2010replicative RNA approach produced more iCS, which had cardiomyocyte differentiation ability and therapeutic effects on the mouse model of MI with comparable levels with endogenous cardiospheres and iCS generated with retrovirus. In addition, the CXCR4 (C\u2010X\u2010C chemokine receptor 4) positive subpopulation of iCS derived cells (iCSDC) delivered by intravenous injection was found to have similar therapeutic effects with intramyocardial injection on the mouse model of MI, representing a safer delivery approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Thus, the optimized strategy for iCS generation is safer and has more therapeutic potentials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.13041","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T12:14:15Z","timestamp":1620130455000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic effects of CXCR4<sup>+<\/sup> subpopulation of transgene\u2010free induced cardiosphere\u2010derived cells on experimental myocardial infarction"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-4603","authenticated-orcid":false,"given":"Jianyong","family":"Xu","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimei","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Mai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbo","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Immunology Health Science Center Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32335-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60107-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-018-0013-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.106"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034250"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0042-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.02.001"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2438"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.12.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15272"},{"issue":"9","key":"e_1_2_9_14_1","first-page":"I150","article-title":"Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials","volume":"112","author":"Hou D","year":"2005","journal-title":"Circulation"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000162100.52009.38"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.08.033"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.02.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.197723"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.11.010"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300374"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172482"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1426"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.06.001"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103509108"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1684"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.097"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-128546"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.11.029"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx203"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13041","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.13041","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T20:21:12Z","timestamp":1692476472000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.13041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,4]]},"references-count":28,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/cpr.13041"],"URL":"https:\/\/doi.org\/10.1111\/cpr.13041","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,4]]},"assertion":[{"value":"2020-09-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13041"}}