{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:14:27Z","timestamp":1777893267604,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["#19-15-00384 and #16-15-00181"],"award-info":[{"award-number":["#19-15-00384 and #16-15-00181"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24\u201328%; 0.17\u20130.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.<\/jats:p>","DOI":"10.3390\/ijms21249603","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T22:12:06Z","timestamp":1608156726000},"page":"9603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction"],"prefix":"10.3390","volume":"21","author":[{"given":"Konstantin V.","family":"Dergilev","sequence":"first","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny K.","family":"Shevchenko","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"},{"name":"Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoya I.","family":"Tsokolaeva","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"},{"name":"Research Institute of General Reanimatology, Russian Academy of Medical Sciences, Moscow 107031, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2345-3681","authenticated-orcid":false,"given":"Irina B.","family":"Beloglazova","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-3670","authenticated-orcid":false,"given":"Ekaterina S.","family":"Zubkova","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-0018","authenticated-orcid":false,"given":"Maria A.","family":"Boldyreva","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail Yu.","family":"Menshikov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizaveta I.","family":"Ratner","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Penkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yelena V.","family":"Parfyonova","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia"},{"name":"Faculty of Medicine, Lomonosov Moscow State University, Moscow 119991, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1001\/jamacardio.2016.2225","article-title":"Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review","volume":"1","author":"Nguyen","year":"2016","journal-title":"JAMA Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/sctm.18-0120","article-title":"Safety and Efficacy of Adult Stem Cell Therapy for Acute Myocardial Infarction and Ischemic Heart Failure (SafeCell Heart): A Systematic Review and Meta-Analysis","volume":"7","author":"Lalu","year":"2018","journal-title":"Stem Cells Transl. 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