{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:43:34Z","timestamp":1769165014244,"version":"3.49.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FORUN Program of Rostock University Medical Centre","award":["889006"],"award-info":[{"award-number":["889006"]}]},{"name":"FORUN Program of Rostock University Medical Centre","award":["889001"],"award-info":[{"award-number":["889001"]}]},{"name":"FORUN Program of Rostock University Medical Centre","award":["889003"],"award-info":[{"award-number":["889003"]}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["VIP+ 00240"],"award-info":[{"award-number":["VIP+ 00240"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU Structural Fund","award":["ESF\/14-BM-A55-0024\/18"],"award-info":[{"award-number":["ESF\/14-BM-A55-0024\/18"]}]},{"name":"Josef and K\u00e4the Klinz Foundation","award":["T319\/29737\/2017"],"award-info":[{"award-number":["T319\/29737\/2017"]}]},{"DOI":"10.13039\/100004875","name":"DFG","doi-asserted-by":"publisher","award":["DA1296\/6-1"],"award-info":[{"award-number":["DA1296\/6-1"]}],"id":[{"id":"10.13039\/100004875","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["EFRE UHROM 16"],"award-info":[{"award-number":["EFRE UHROM 16"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL\/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.<\/jats:p>","DOI":"10.3390\/cells9081825","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T07:45:57Z","timestamp":1596440757000},"page":"1825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cardiomyocyte Transplantation after Myocardial Infarction Alters the Immune Response in the Heart"],"prefix":"10.3390","volume":"9","author":[{"given":"Praveen","family":"Vasudevan","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"},{"name":"Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany"},{"name":"Department of Operative Dentistry and Periodontology, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1887-4772","authenticated-orcid":false,"given":"Markus","family":"Wolfien","sequence":"additional","affiliation":[{"name":"Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2821-2323","authenticated-orcid":false,"given":"Heiko","family":"Lemcke","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"},{"name":"Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cajetan Immanuel","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6287-4916","authenticated-orcid":false,"given":"Anna","family":"Skorska","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"},{"name":"Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7161-3459","authenticated-orcid":false,"given":"Ralf","family":"Gaebel","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"},{"name":"Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Koczan","sequence":"additional","affiliation":[{"name":"Core Facility for Microarray Analysis, Institute for Immunology, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-3132","authenticated-orcid":false,"given":"Tobias","family":"Lindner","sequence":"additional","affiliation":[{"name":"Core Facility Multimodal Small Animal Imaging, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robby","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Core Facility for Cell Sorting &amp; Cell Analysis, Laboratory for Clinical Immunology, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigitte","family":"Vollmar","sequence":"additional","affiliation":[{"name":"Rudolf-Zenker-Institute for Experimental Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd Joachim","family":"Krause","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Wolkenhauer","sequence":"additional","affiliation":[{"name":"Department of Systems Biology and Bioinformatics, Institute of Computer Science, University of Rostock, 18057 Rostock, Germany"},{"name":"Stellenbosch Institute of Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch 7602, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Operative Dentistry and Periodontology, Rostock University Medical Centre, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustav","family":"Steinhoff","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"},{"name":"Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"David","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Rostock University Medical Centre, 18057 Rostock, Germany"},{"name":"Department of Life, Light and Matter, University of Rostock, 18059 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e146","DOI":"10.1161\/CIR.0000000000000485","article-title":"Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association","volume":"135","author":"Benjamin","year":"2017","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2017.10.007","article-title":"Stem cells and heart disease\u2014Brake or accelerator?","volume":"120","author":"Steinhoff","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(2017). A futile cycle in cell therapy. Nat. Biotechnol., 35, 291.","DOI":"10.1038\/nbt.3857"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/nature13233","article-title":"Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts","volume":"510","author":"Chong","year":"2014","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.stem.2014.06.009","article-title":"Immune Modulation of Stem Cells and Regeneration","volume":"15","author":"Aurora","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16029","DOI":"10.1073\/pnas.1406508111","article-title":"Distinct macrophage lineages contribute to disparate patterns of cardiac recovery and remodeling in the neonatal and adult heart","volume":"111","author":"Lavine","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/j.jacc.2013.07.057","article-title":"Macrophage subpopulations are essential for infarct repair with and without stem cell therapy","volume":"62","author":"Holbova","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jneuroim.2010.12.004","article-title":"Immunoregulatory function of bone marrow mesenchymal stem cells in EAE depends on their differentiation state and secretion of PGE2","volume":"233","author":"Matysiak","year":"2011","journal-title":"J. Neuroimmunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1182\/blood-2005-07-2657","article-title":"Human mesenchymal stem cells modulate B-cell functions","volume":"107","author":"Corcione","year":"2006","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1634\/stemcells.2004-0359","article-title":"Interactions between human mesenchymal stem cells and natural killer cells","volume":"24","author":"Sotiropoulou","year":"2006","journal-title":"Stem Cells"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCRESAHA.117.305365","article-title":"Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Insights Into Molecular, Cellular, and Functional Phenotypes","volume":"117","author":"Karakikes","year":"2015","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s41232-019-0110-4","article-title":"Toward the realization of cardiac regenerative medicine using pluripotent stem cells","volume":"40","author":"Kishino","year":"2020","journal-title":"Inflamm. Regen."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Vasudevan, P., Gaebel, R., D\u00f6ring, P., M\u00fcller, P., Lemcke, H., Stenzel, J., Lindner, T., Kurth, J., Steinhoff, G., and Vollmar, B. (2019). 18F-FDG PET-Based Imaging of Myocardial Inflammation Predicts a Functional Outcome Following Transplantation of mESC-Derived Cardiac Induced Cells in a Mouse Model of Myocardial Infarction. Cells, 8.","DOI":"10.3390\/cells8121613"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Heiberg, E., Sj\u00f6gren, J., Ugander, M., Carlsson, M., Engblom, H., and Arheden, H. (2010). Design and validation of Segment\u2014Freely available software for cardiovascular image analysis. BMC Med. Imaging, 10.","DOI":"10.1186\/1471-2342-10-1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180145","DOI":"10.1038\/sdata.2018.145","article-title":"Microarray data of transcriptome shifts in blood cell subsets during S1P receptor modulator therapy","volume":"5","author":"Koczan","year":"2018","journal-title":"Sci. Data"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W147","DOI":"10.1093\/nar\/gkw419","article-title":"Heatmapper: Web-enabled heat mapping for all","volume":"44","author":"Babicki","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s10456-014-9435-4","article-title":"Angiopoietin-like 7, a novel pro-angiogenetic factor over-expressed in cancer","volume":"17","author":"Parri","year":"2014","journal-title":"Angiogenesis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41590-018-0272-2","article-title":"Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction","volume":"20","author":"Dick","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.immuni.2013.11.019","article-title":"Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation","volume":"40","author":"Epelman","year":"2014","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.43882","article-title":"Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury","volume":"8","author":"Farbehi","year":"2019","journal-title":"Elife"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1084\/jem.20061469","article-title":"Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium","volume":"203","author":"Kolossov","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/nbt1327","article-title":"Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts","volume":"25","author":"Laflamme","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/nbt1014","article-title":"Electromechanical integration of cardiomyocytes derived from human embryonic stem cells","volume":"22","author":"Kehat","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1161\/CIRCRESAHA.107.153643","article-title":"Electrophysiological maturation and integration of murine fetal cardiomyocytes after transplantation","volume":"101","author":"Halbach","year":"2007","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19111","DOI":"10.1038\/srep19111","article-title":"Enhanced engraftment, proliferation, and therapeutic potential in heart using optimized human iPSC-derived cardiomyocytes","volume":"6","author":"Funakoshi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/stem.1089","article-title":"Pluripotent stem cell-engineered cell sheets reassembled with defined cardiovascular populations ameliorate reduction in infarct heart function through cardiomyocyte-mediated neovascularization","volume":"30","author":"Masumoto","year":"2012","journal-title":"Stem Cells"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1016\/j.jacc.2007.07.054","article-title":"Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts","volume":"50","author":"Caspi","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.yjmcc.2012.06.007","article-title":"Time-course of the electrophysiological maturation and integration of transplanted cardiomyocytes","volume":"53","author":"Halbach","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1161\/01.CIR.0000013782.76324.92","article-title":"Rebuilding a Damaged Heart: Long-Term Survival of Transplanted Neonatal Rat Cardiomyocytes After Myocardial Infarction and Effect on Cardiac Function","volume":"105","year":"2002","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nature19815","article-title":"Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts","volume":"538","author":"Shiba","year":"2016","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1161\/CIRCRESAHA.117.310803","article-title":"Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium","volume":"121","author":"Tachibana","year":"2017","journal-title":"Circ. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1161\/CIRCRESAHA.117.311578","article-title":"Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates","volume":"122","author":"Zhu","year":"2018","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nbt.4162","article-title":"Human embryonic stem cell\u2013derived cardiomyocytes restore function in infarcted hearts of non-human primates","volume":"36","author":"Liu","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1161\/hh2401.100741","article-title":"Intrinsic diurnal variations in cardiac metabolism and contractile function","volume":"89","author":"Young","year":"2001","journal-title":"Circ. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24254","DOI":"10.1074\/jbc.M601704200","article-title":"The circadian clock within the cardiomyocyte is essential for responsiveness of the heart to fatty acids","volume":"281","author":"Durgan","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1126\/science.1195027","article-title":"Circadian integration of metabolism and energetics","volume":"330","author":"Bass","year":"2010","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3109\/07420529908998730","article-title":"Biologic rhythms in the immune system","volume":"16","author":"Haus","year":"1999","journal-title":"Chronobiol. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1126\/science.1240636","article-title":"Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes","volume":"341","author":"Nguyen","year":"2013","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.yjmcc.2017.08.009","article-title":"Neonatal rat cardiomyocytes as an in vitro model for circadian rhythms in the heart","volume":"112","author":"Dierickx","year":"2017","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.15252\/embr.201743897","article-title":"Circadian networks in human embryonic stem cell-derived cardiomyocytes","volume":"18","author":"Dierickx","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/s41586-019-1802-2","article-title":"An acute immune response underlies the benefit of cardiac stem cell therapy","volume":"577","author":"Vagnozzi","year":"2020","journal-title":"Nature"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/8\/1825\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:51Z","timestamp":1760176431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/8\/1825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,3]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["cells9081825"],"URL":"https:\/\/doi.org\/10.3390\/cells9081825","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,3]]}}}