{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:40:33Z","timestamp":1792100433540,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["332652"],"award-info":[{"award-number":["332652"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ventricular remodeling following myocardial infarction (MI) is a major cause of heart failure, a condition prevalent in older individuals. Following MI, immune cells are mobilized to the myocardium from peripheral lymphoid organs and play an active role in orchestrating repair. While the effect of aging on mouse bone marrow (BM) has been studied, less is known about how aging affects human BM cells and their ability to regulate repair processes. In this study, we investigate the effect aging has on human BM cell responses post\u2010MI using a humanized chimeric mouse model. BM samples were collected from middle aged (mean age 56.4\u00a0\u00b1\u00a00.97) and old (mean age 72.7\u00a0\u00b1\u00a00.59) patients undergoing cardiac surgery, CD34<jats:sup>+\/\u2212<\/jats:sup> cells were isolated, and NOD\u2010scid\u2010IL2r\u03b3<jats:sup>null<\/jats:sup> (NSG) mice were reconstituted. Three months following reconstitution, the animals were examined at baseline or subjected to coronary artery ligation (MI). Younger patient cells exhibited greater repopulation capacity in the BM, blood, and spleen as well as greater lymphoid cell production. Following MI, CD34<jats:sup>+<\/jats:sup> cell age impacted donor and host cellular responses. Mice reconstituted with younger CD34<jats:sup>+<\/jats:sup> cells exhibited greater human CD45<jats:sup>+<\/jats:sup> recruitment to the heart compared to mice reconstituted with old cells. Increased cellular responses were primarily driven by T\u2010cell recruitment, and these changes corresponded with greater human IFNy levels and reduced mouse IL\u20101\u03b2 in the heart. Age\u2010dependent changes in BM function led to significantly lower survival, increased infarct expansion, impaired host cell responses, and reduced function by 4w post\u2010MI. In contrast, younger CD34<jats:sup>+<\/jats:sup> cells helped to limit remodeling and preserve function post\u2010MI.<\/jats:p>","DOI":"10.1111\/acel.13494","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T16:19:59Z","timestamp":1633709999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Aging impairs human bone marrow function and cardiac repair following myocardial infarction in a humanized chimeric mouse"],"prefix":"10.1111","volume":"20","author":[{"given":"Tina B.","family":"Marvasti","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal J.","family":"Alibhai","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Wlodarek","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Weisel","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"},{"name":"Division of Cardiovascular Surgery Department of Surgery University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Cusimano","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"},{"name":"Division of Cardiovascular Surgery Department of Surgery University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maral","family":"Ouzounian","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"},{"name":"Division of Cardiovascular Surgery Department of Surgery University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence","family":"Yau","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"},{"name":"Division of Cardiovascular Surgery Department of Surgery University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-060X","authenticated-orcid":false,"given":"Ren\u2010Ke","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery Peter Munk Cardiac Centre Toronto General Hospital Research Institute University Health Network Toronto Ontario Canada"},{"name":"Division of Cardiovascular Surgery Department of Surgery University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102838"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13103"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-020-10065-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-005-4088-0"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2015.07.004"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.584538"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0860"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz092"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.06.007"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.044164"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2011.00675.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13026"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41756"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2019.05.037"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2005.02.036"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116110108"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303577"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.06.016"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123859"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113653"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081894"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13312"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1802-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.303895"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1681-3"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13494","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.13494","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.13494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:46:14Z","timestamp":1693201574000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.13494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/acel.13494"],"URL":"https:\/\/doi.org\/10.1111\/acel.13494","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,6]]},"assertion":[{"value":"2021-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13494"}}