{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:29:05Z","timestamp":1790072945497,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Natural Science Grant of China","award":["81470456"],"award-info":[{"award-number":["81470456"]}]},{"name":"National Natural Science Grant of China","award":["81671882"],"award-info":[{"award-number":["81671882"]}]},{"name":"National Natural Science Grant of China","award":["81700259"],"award-info":[{"award-number":["81700259"]}]},{"name":"National Natural Science Grant of China","award":["81871113"],"award-info":[{"award-number":["81871113"]}]},{"name":"National Natural Science Grant of China","award":["81871599"],"award-info":[{"award-number":["81871599"]}]},{"name":"Qinghai Provincial Natural Science Fund","award":["2017-ZJ-769"],"award-info":[{"award-number":["2017-ZJ-769"]}]},{"name":"Guangdong Provincial People's Hospital Grant for Talent Introduction","award":["Y012018144"],"award-info":[{"award-number":["Y012018144"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Accumulating evidence has shown that mesenchymal stem cell (MSC)\u2010derived exosomes (exo) mediate cardiac repair following myocardial infarction (MI). Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, plays a critical role in regulating cell homeostasis. This study aimed to investigate the cardioprotective effects of exo secreted from bone marrow\u2010MSCs (BM\u2010MSCs) overexpressing MIF in a rat model of MI. MIF plasmid was transducted in BM\u2010MSCs. Exo were isolated from the supernatants of BM\u2010MSCs and MIF\u2010BM\u2010MSCs, respectively. The morphology of mitochondria in neonatal mice cardiomyocytes (NRCMs) was determined by MitoTracker staining. The apoptosis of NRCMs was examined by deoxynucleotidyl transferase\u2010mediated dUTP nick end\u2010labeling. BM\u2010MSC\u2010exo and MIF\u2010BM\u2010MSC\u2010exo were intramuscularly injected into the peri\u2010infarct region in a rat model of MI. The heart function of rats was assessed by echocardiography. The expression of MIF was greatly enhanced in MIF\u2010BM\u2010MSCs compared with BM\u2010MSCs. Both BM\u2010MSC\u2010exo and MIF\u2010BM\u2010MSC\u2010exo expressed CD63 and CD81. NRCMs treated with MIF\u2010BM\u2010MSC\u2010exo exhibited less mitochondrial fragmentation and cell apoptosis under hypoxia\/serum deprivation (H\/SD) challenge than those treated with BM\u2010MSC\u2010exo via activating adenosine 5\u2032\u2010monophosphate\u2010activated protein kinase signaling. Moreover, these effects were partially abrogated by Compound C. Injection of BM\u2010MSC\u2010exo or MIF\u2010BM\u2010MSC\u2010exo greatly restored heart function in a rat model of MI. Compared with BM\u2010MSC\u2010exo, injection of MIF\u2010BM\u2010MSC\u2010exo was associated with enhanced heart function, reduced heart remodeling, less cardiomyocyte mitochondrial fragmentation, reactive oxygen species generation, and apoptosis. Our study reveals a new mechanism of MIF\u2010BM\u2010MSC\u2010exo\u2010based therapy for MI and provides a novel strategy for cardiovascular disease treatment.<\/jats:p>","DOI":"10.1002\/jcp.29456","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T04:31:39Z","timestamp":1579581099000},"page":"8010-8022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["Exosomes from mesenchymal stem cells overexpressing MIF enhance myocardial repair"],"prefix":"10.1002","volume":"235","author":[{"given":"Xiaolin","family":"Liu","sequence":"first","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Liang","sequence":"additional","affiliation":[{"name":"Clinical Translational Medical Research Center, Shanghai East Hospital Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohan","family":"Fan","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"},{"name":"Department of Emergency and Critical Care Medicine, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0125-3926","authenticated-orcid":false,"given":"Fengxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Section of Pacing and Electrophysiology, Division of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0039"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101512-122326"},{"issue":"4","key":"e_1_2_9_4_1","first-page":"367","article-title":"Paracrine action accounts for marked protection of ischemic heart by Akt\u2010modified mesenchymal stem cells","volume":"11","author":"Gnecchi M.","year":"2005","journal-title":"Nature Medicine (New York, NY, United States)"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.08.019"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13560"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt546"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305432"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2012.08.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801690R"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000480317"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.04.012"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000488635"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2016-0038"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2013.0294"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.05.021"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.44"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24803"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191616"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-4397-0_12"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.61"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0386"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8619"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.09.024"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2016.1153951"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.01.015"},{"issue":"2","key":"e_1_2_9_27_1","first-page":"1127","article-title":"Macrophage migration inhibitory factor rescues mesenchymal stem cells from doxorubicin\u2010induced senescence though the PI3K\u2010Akt signaling pathway","volume":"41","author":"Xia W.","year":"2018","journal-title":"International Journal of Molecular Medicine"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0076-3"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22488"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2016.11.019"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.07.003"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.12.043"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00547"},{"issue":"1","key":"e_1_2_9_34_1","first-page":"74","article-title":"Absence of NUCKS augments paracrine effects of mesenchymal stem cells\u2010mediated cardiac protection","volume":"356","author":"Zhang Y.","year":"2017","journal-title":"Experimental Cell Research"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11235"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.03.024"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.07.034"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4079041"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0552-7"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12413"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19979"},{"issue":"8","key":"e_1_2_9_42_1","first-page":"1659","article-title":"Myocardial reparative functions of exosomes from mesenchymal stem cells are enhanced by hypoxia treatment of the cells via transferring microRNA\u2010210 in an nSMase2\u2010dependent way","volume":"46","author":"Zhu J.","year":"2018","journal-title":"Artificial Cells, Nanomedicine, and Biotechnology"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.29456","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29456","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.29456","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T17:01:57Z","timestamp":1732122117000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.29456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,20]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/jcp.29456"],"URL":"https:\/\/doi.org\/10.1002\/jcp.29456","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,20]]},"assertion":[{"value":"2019-04-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}