{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T14:45:25Z","timestamp":1772721925761,"version":"3.50.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["ID1105271"],"award-info":[{"award-number":["ID1105271"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP100046"],"award-info":[{"award-number":["APP100046"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["ID100848"],"award-info":[{"award-number":["ID100848"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["ID1100463"],"award-info":[{"award-number":["ID1100463"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have previously reported a subpopulation of mesenchymal stromal cells (MSCs) within the platelet-derived growth factor receptor-alpha (PDGFR\u03b1)\/CD90 co-expressing cardiac interstitial and adventitial cell fraction. Here we further characterise PDGFR\u03b1\/CD90-expressing cardiac MSCs (PDGFR\u03b1\u2009+\u2009cMSCs) and use human telomerase reverse transcriptase (hTERT) over-expression to increase cMSCs ability to repair the heart after induced myocardial infarction. hTERT over-expression in PDGFR\u03b1\u2009+\u2009cardiac MSCs (hTERT\u2009+\u2009PDGFR\u03b1\u2009+\u2009cMSCs) modulates cell differentiation, proliferation, survival and angiogenesis related genes. <jats:italic>In vivo<\/jats:italic>, transplantation of hTERT\u2009+\u2009PDGFR\u03b1\u2009+\u2009cMSCs in athymic rats significantly increased left ventricular function, reduced scar size, increased angiogenesis and proliferation of both cardiomyocyte and non-myocyte cell fractions four weeks after myocardial infarction. In contrast, transplantation of mutant hTERT\u2009+\u2009PDGFR\u03b1\u2009+\u2009cMSCs (which generate catalytically-inactive telomerase) failed to replicate this cardiac functional improvement, indicating a telomerase-dependent mechanism. There was no hTERT\u2009+\u2009PDGFR\u03b1\u2009+\u2009cMSCs engraftment 14 days after transplantation indicating functional improvement occurred by paracrine mechanisms. Mass spectrometry on hTERT\u2009+\u2009PDGFR\u03b1\u2009+\u2009cMSCs conditioned media showed increased proteins associated with matrix modulation, angiogenesis, cell proliferation\/survival\/adhesion and innate immunity function. Our study shows that hTERT can activate pro-regenerative signalling within PDGFR\u03b1\u2009+\u2009cMSCs and enhance cardiac repair after myocardial infarction. An increased understanding of hTERT\u2019s role in mesenchymal stromal cells from various organs will favourably impact clinical regenerative and anti-cancer therapies.<\/jats:p>","DOI":"10.1038\/s41598-019-47022-w","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T10:02:40Z","timestamp":1563789760000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Enhanced cardiac repair by telomerase reverse transcriptase over-expression in human cardiac mesenchymal stromal cells"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-7341","authenticated-orcid":false,"given":"Thi Yen Loan","family":"Le","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilda A.","family":"Pickett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2331-7011","authenticated-orcid":false,"given":"Joshua W. K.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujitha","family":"Thavapalachandran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sindhu","family":"Igoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sile F.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0656-2816","authenticated-orcid":false,"given":"Melad","family":"Farraha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5315-794X","authenticated-orcid":false,"given":"Holly K.","family":"Voges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristobal G.","family":"dos Remedios","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-5501","authenticated-orcid":false,"given":"Tracy M.","family":"Bryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eddy","family":"Kizana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5201-4856","authenticated-orcid":false,"given":"James J. H.","family":"Chong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"key":"47022_CR1","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.jacc.2013.11.053","volume":"63","author":"AP Ambrosy","year":"2014","unstructured":"Ambrosy, A. P. et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol 63, 1123\u20131133, https:\/\/doi.org\/10.1016\/j.jacc.2013.11.053 (2014).","journal-title":"J Am Coll Cardiol"},{"key":"47022_CR2","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1161\/CIRCRESAHA.115.307778","volume":"118","author":"AR Pinto","year":"2016","unstructured":"Pinto, A. R. et al. Revisiting Cardiac Cellular Composition. Circ Res 118, 400\u2013409, https:\/\/doi.org\/10.1161\/CIRCRESAHA.115.307778 (2016).","journal-title":"Circ Res"},{"key":"47022_CR3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1161\/CIRCRESAHA.113.302895","volume":"114","author":"E Matsa","year":"2014","unstructured":"Matsa, E., Sallam, K. & Wu, J. C. Cardiac stem cell biology: glimpse of the past, present, and future. Circ Res 114, 21\u201327, https:\/\/doi.org\/10.1161\/CIRCRESAHA.113.302895 (2014).","journal-title":"Circ Res"},{"key":"47022_CR4","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.diff.2016.06.004","volume":"92","author":"MB Furtado","year":"2016","unstructured":"Furtado, M. B., Costa, M. W. & Rosenthal, N. A. The cardiac fibroblast: Origin, identity and role in homeostasis and disease. Differentiation; research in biological diversity 92, 93\u2013101, https:\/\/doi.org\/10.1016\/j.diff.2016.06.004 (2016).","journal-title":"Differentiation; research in biological diversity"},{"key":"47022_CR5","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.ajpath.2011.03.036","volume":"179","author":"D Cesselli","year":"2011","unstructured":"Cesselli, D. et al. Effects of age and heart failure on human cardiac stem cell function. Am J Pathol 179, 349\u2013366, https:\/\/doi.org\/10.1016\/j.ajpath.2011.03.036 (2011).","journal-title":"Am J Pathol"},{"key":"47022_CR6","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1161\/CIRCRESAHA.113.302302","volume":"113","author":"S Mohsin","year":"2013","unstructured":"Mohsin, S. et al. Rejuvenation of human cardiac progenitor cells with Pim-1 kinase. Circ Res 113, 1169\u20131179, https:\/\/doi.org\/10.1161\/CIRCRESAHA.113.302302 (2013).","journal-title":"Circ Res"},{"key":"47022_CR7","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1161\/CIRCRESAHA.116.310316","volume":"120","author":"C Bar","year":"2017","unstructured":"Bar, C. & Thum, T. Changing Direction: From Therapeutic Telomerase Inhibition to Activation? Circ Res 120, 1393\u20131395, https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.310316 (2017).","journal-title":"Circ Res"},{"key":"47022_CR8","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1093\/eurheartj\/ehq450","volume":"32","author":"R Madonna","year":"2011","unstructured":"Madonna, R., De Caterina, R., Willerson, J. T. & Geng, Y. J. Biologic function and clinical potential of telomerase and associated proteins in cardiovascular tissue repair and regeneration. Eur Heart J 32, 1190\u20131196, https:\/\/doi.org\/10.1093\/eurheartj\/ehq450 (2011).","journal-title":"Eur Heart J"},{"key":"47022_CR9","doi-asserted-by":"publisher","first-page":"e005086","DOI":"10.1161\/JAHA.116.005086","volume":"6","author":"M Sharifi-Sanjani","year":"2017","unstructured":"Sharifi-Sanjani, M. et al. Cardiomyocyte-Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans. J Am Heart Assoc 6, e005086, https:\/\/doi.org\/10.1161\/JAHA.116.005086 (2017).","journal-title":"J Am Heart Assoc"},{"key":"47022_CR10","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1161\/CIRCRESAHA.113.301690","volume":"113","author":"R Madonna","year":"2013","unstructured":"Madonna, R. et al. Transplantation of mesenchymal cells rejuvenated by the overexpression of telomerase and myocardin promotes revascularization and tissue repair in a murine model of hindlimb ischemia. Circ Res 113, 902\u2013914, https:\/\/doi.org\/10.1161\/CIRCRESAHA.113.301690 (2013).","journal-title":"Circ Res"},{"key":"47022_CR11","first-page":"14447","volume":"8","author":"SH Li","year":"2015","unstructured":"Li, S. H. et al. Exogenous hTERT gene transfected endothelial progenitor cells from bone marrow promoted angiogenesis in ischemic myocardium of rats. Int J Clin Exp Med 8, 14447\u201314453 (2015).","journal-title":"Int J Clin Exp Med"},{"key":"47022_CR12","doi-asserted-by":"publisher","first-page":"e0147853","DOI":"10.1371\/journal.pone.0147853","volume":"11","author":"JH Kim","year":"2016","unstructured":"Kim, J. H. et al. Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses. PLoS One 11, e0147853, https:\/\/doi.org\/10.1371\/journal.pone.0147853 (2016).","journal-title":"PLoS One"},{"key":"47022_CR13","doi-asserted-by":"publisher","first-page":"10308","DOI":"10.1073\/pnas.191169098","volume":"98","author":"H Oh","year":"2001","unstructured":"Oh, H. et al. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Proc Natl Acad Sci USA 98, 10308\u201310313, https:\/\/doi.org\/10.1073\/pnas.191169098 (2001).","journal-title":"Proc Natl Acad Sci USA"},{"key":"47022_CR14","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/emmm.201200245","volume":"4","author":"B Bernardes de Jesus","year":"2012","unstructured":"Bernardes de Jesus, B. et al. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO molecular medicine 4, 691\u2013704, https:\/\/doi.org\/10.1002\/emmm.201200245 (2012).","journal-title":"EMBO molecular medicine"},{"key":"47022_CR15","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.stem.2011.10.002","volume":"9","author":"JJ Chong","year":"2011","unstructured":"Chong, J. J. et al. Adult cardiac-resident MSC-like stem cells with a proepicardial origin. Cell Stem Cell 9, 527\u2013540, https:\/\/doi.org\/10.1016\/j.stem.2011.10.002 (2011).","journal-title":"Cell Stem Cell"},{"key":"47022_CR16","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1089\/scd.2012.0542","volume":"22","author":"JJ Chong","year":"2013","unstructured":"Chong, J. J. et al. Progenitor cells identified by PDGFR-alpha expression in the developing and diseased human heart. Stem Cells Dev 22, 1932\u20131943, https:\/\/doi.org\/10.1089\/scd.2012.0542 (2013).","journal-title":"Stem Cells Dev"},{"key":"47022_CR17","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1089\/scd.2017.0082","volume":"27","author":"TYL Le","year":"2018","unstructured":"Le, T. Y. L. et al. Platelet-Derived Growth Factor Receptor-Alpha Expressing Cardiac Progenitor Cells Can Be Derived from Previously Cryopreserved Human Heart Samples. Stem Cells Dev 27, 184\u2013198, https:\/\/doi.org\/10.1089\/scd.2017.0082 (2018).","journal-title":"Stem Cells Dev"},{"key":"47022_CR18","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1161\/01.CIR.83.2.504","volume":"83","author":"J Schaper","year":"1991","unstructured":"Schaper, J. et al. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 83, 504\u2013514, https:\/\/doi.org\/10.1161\/01.CIR.83.2.504 (1991).","journal-title":"Circulation"},{"key":"47022_CR19","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/mus.22228","volume":"44","author":"N Carboni","year":"2011","unstructured":"Carboni, N. et al. Dilated cardiomyopathy with conduction defects in a patient with partial merosin deficiency due to mutations in the laminin-alpha2-chain gene: a chance association or a novel phenotype? Muscle & nerve 44, 826\u2013828, https:\/\/doi.org\/10.1002\/mus.22228 (2011).","journal-title":"Muscle & nerve"},{"key":"47022_CR20","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/nature08137","volume":"460","author":"JI Park","year":"2009","unstructured":"Park, J. I. et al. Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460, 66\u201372, https:\/\/doi.org\/10.1038\/nature08137 (2009).","journal-title":"Nature"},{"key":"47022_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/srep22886","volume":"6","author":"H Liu","year":"2016","unstructured":"Liu, H. et al. hTERT promotes cell adhesion and migration independent of telomerase activity. Sci Rep 6, 22886, https:\/\/doi.org\/10.1038\/srep22886 (2016).","journal-title":"Sci Rep"},{"key":"47022_CR22","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/sj.leu.2402962","volume":"17","author":"S Zimmermann","year":"2003","unstructured":"Zimmermann, S. et al. Lack of telomerase activity in human mesenchymal stem cells. Leukemia 17, 1146\u20131149, https:\/\/doi.org\/10.1038\/sj.leu.2402962 (2003).","journal-title":"Leukemia"},{"key":"47022_CR23","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","volume":"119","author":"SD Prabhu","year":"2016","unstructured":"Prabhu, S. D. & Frangogiannis, N. G. The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis. Circ Res 119, 91\u2013112, https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.303577 (2016).","journal-title":"Circ Res"},{"key":"47022_CR24","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/nrd.2016.89","volume":"15","author":"RG Gourdie","year":"2016","unstructured":"Gourdie, R. G., Dimmeler, S. & Kohl, P. Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease. Nat Rev Drug Discov 15, 620\u2013638, https:\/\/doi.org\/10.1038\/nrd.2016.89 (2016).","journal-title":"Nat Rev Drug Discov"},{"key":"47022_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6863","volume":"5","author":"C Bar","year":"2014","unstructured":"Bar, C. et al. Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction. Nat Commun 5, 5863, https:\/\/doi.org\/10.1038\/ncomms6863 (2014).","journal-title":"Nat Commun"},{"key":"47022_CR26","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1242\/dev.143966","volume":"144","author":"HK Voges","year":"2017","unstructured":"Voges, H. K. et al. Development of a human cardiac organoid injury model reveals innate regenerative potential. Development 144, 1118\u20131127, https:\/\/doi.org\/10.1242\/dev.143966 (2017).","journal-title":"Development"},{"key":"47022_CR27","doi-asserted-by":"publisher","first-page":"E8372","DOI":"10.1073\/pnas.1707316114","volume":"114","author":"RJ Mills","year":"2017","unstructured":"Mills, R. J. et al. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc Natl Acad Sci USA 114, E8372\u2013E8381, https:\/\/doi.org\/10.1073\/pnas.1707316114 (2017).","journal-title":"Proc Natl Acad Sci USA"},{"key":"47022_CR28","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.1101\/gad.11.23.3109","volume":"11","author":"L Harrington","year":"1997","unstructured":"Harrington, L. et al. Human telomerase contains evolutionarily conserved catalytic and structural subunits. Genes Dev 11, 3109\u20133115, https:\/\/doi.org\/10.1101\/gad.11.23.3109 (1997).","journal-title":"Genes Dev"},{"key":"47022_CR29","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1172\/JCI83822","volume":"127","author":"M Nakaya","year":"2017","unstructured":"Nakaya, M. et al. Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction. J Clin Invest 127, 383\u2013401, https:\/\/doi.org\/10.1172\/JCI83822 (2017).","journal-title":"J Clin Invest"},{"key":"47022_CR30","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1182\/blood-2006-07-036202","volume":"110","author":"K Grote","year":"2007","unstructured":"Grote, K. et al. The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration. Blood 110, 877\u2013885, https:\/\/doi.org\/10.1182\/blood-2006-07-036202 (2007).","journal-title":"Blood"},{"key":"47022_CR31","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1016\/j.jacc.2011.08.033","volume":"58","author":"EA Liehn","year":"2011","unstructured":"Liehn, E. A. et al. Double-edged role of the CXCL12\/CXCR4 axis in experimental myocardial infarction. J Am Coll Cardiol 58, 2415\u20132423, https:\/\/doi.org\/10.1016\/j.jacc.2011.08.033 (2011).","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"47022_CR32","doi-asserted-by":"publisher","first-page":"e12931","DOI":"10.1111\/acel.12931","volume":"18","author":"Fiona C. Lewis\u2010McDougall","year":"2019","unstructured":"Lewis-McDougall, F. C. et al. Aged-senescent cells contribute to impaired heart regeneration. Aging Cell, e12931, https:\/\/doi.org\/10.1111\/acel.12931 (2019).","journal-title":"Aging Cell"},{"key":"47022_CR33","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/nrcardio.2017.57","volume":"14","author":"MD Tallquist","year":"2017","unstructured":"Tallquist, M. D. & Molkentin, J. D. Redefining the identity of cardiac fibroblasts. Nat Rev Cardiol 14, 484\u2013491, https:\/\/doi.org\/10.1038\/nrcardio.2017.57 (2017).","journal-title":"Nat Rev Cardiol"},{"key":"47022_CR34","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1161\/CIRCRESAHA.110.235531","volume":"108","author":"CL Smith","year":"2011","unstructured":"Smith, C. L., Baek, S. T., Sung, C. Y. & Tallquist, M. D. Epicardial-derived cell epithelial-to-mesenchymal transition and fate specification require PDGF receptor signaling. Circ Res 108, e15\u201326, https:\/\/doi.org\/10.1161\/CIRCRESAHA.110.235531 (2011).","journal-title":"Circ Res"},{"key":"47022_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12260","volume":"7","author":"O Kanisicak","year":"2016","unstructured":"Kanisicak, O. et al. Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nat Commun 7, 12260, https:\/\/doi.org\/10.1038\/ncomms12260 (2016).","journal-title":"Nat Commun"},{"key":"47022_CR36","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.pharmthera.2009.05.002","volume":"123","author":"KE Porter","year":"2009","unstructured":"Porter, K. E. & Turner, N. A. Cardiac fibroblasts: at the heart of myocardial remodeling. Pharmacol Ther 123, 255\u2013278, https:\/\/doi.org\/10.1016\/j.pharmthera.2009.05.002 (2009).","journal-title":"Pharmacol Ther"},{"key":"47022_CR37","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1161\/CIRCRESAHA.114.302530","volume":"114","author":"MB Furtado","year":"2014","unstructured":"Furtado, M. B. et al. Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair. Circ Res 114, 1422\u20131434, https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.302530 (2014).","journal-title":"Circ Res"},{"key":"47022_CR38","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.stemcr.2014.03.003","volume":"2","author":"N Gago-Lopez","year":"2014","unstructured":"Gago-Lopez, N. et al. THY-1 receptor expression differentiates cardiosphere-derived cells with divergent cardiogenic differentiation potential. Stem Cell Reports 2, 576\u2013591, https:\/\/doi.org\/10.1016\/j.stemcr.2014.03.003 (2014).","journal-title":"Stem Cell Reports"},{"key":"47022_CR39","doi-asserted-by":"publisher","first-page":"e001260","DOI":"10.1161\/JAHA.114.001260","volume":"3","author":"K Cheng","year":"2014","unstructured":"Cheng, K. et al. Relative roles of CD90 and c-kit to the regenerative efficacy of cardiosphere-derived cells in humans and in a mouse model of myocardial infarction. J Am Heart Assoc 3, e001260, https:\/\/doi.org\/10.1161\/JAHA.114.001260 (2014).","journal-title":"J Am Heart Assoc"},{"key":"47022_CR40","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.scr.2011.11.002","volume":"8","author":"EU Alt","year":"2012","unstructured":"Alt, E. U. et al. Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res 8, 215\u2013225, https:\/\/doi.org\/10.1016\/j.scr.2011.11.002 (2012).","journal-title":"Stem Cell Res"},{"key":"47022_CR41","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1002\/cphy.c140082","volume":"5","author":"M Rota","year":"2015","unstructured":"Rota, M., Goichberg, P., Anversa, P. & Leri, A. Aging Effects on Cardiac Progenitor Cell Physiology. Compr Physiol 5, 1775\u20131814, https:\/\/doi.org\/10.1002\/cphy.c140082 (2015).","journal-title":"Compr Physiol"},{"key":"47022_CR42","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1016\/j.jacc.2013.02.071","volume":"61","author":"J Bartunek","year":"2013","unstructured":"Bartunek, J. et al. Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol 61, 2329\u20132338, https:\/\/doi.org\/10.1016\/j.jacc.2013.02.071 (2013).","journal-title":"J Am Coll Cardiol"},{"key":"47022_CR43","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1016\/j.jacc.2016.09.925","volume":"68","author":"S Kulandavelu","year":"2016","unstructured":"Kulandavelu, S. et al. Pim1 Kinase Overexpression Enhances ckit(+) Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine. J Am Coll Cardiol 68, 2454\u20132464, https:\/\/doi.org\/10.1016\/j.jacc.2016.09.925 (2016).","journal-title":"J Am Coll Cardiol"},{"key":"47022_CR44","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1161\/01.CIR.0000027584.85865.B4","volume":"106","author":"S Murasawa","year":"2002","unstructured":"Murasawa, S. et al. Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation 106, 1133\u20131139, https:\/\/doi.org\/10.1161\/01.CIR.0000027584.85865.B4 (2002).","journal-title":"Circulation"},{"key":"47022_CR45","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1126\/science.1115025","volume":"309","author":"I Flores","year":"2005","unstructured":"Flores, I., Cayuela, M. L. & Blasco, M. A. Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 1253\u20131256, https:\/\/doi.org\/10.1126\/science.1115025 (2005).","journal-title":"Science"},{"key":"47022_CR46","doi-asserted-by":"publisher","first-page":"239","DOI":"10.7537\/marslsj080211.30","volume":"8","author":"LR Min","year":"2011","unstructured":"Min, L. R., Ling, B. H., Wu, D. Y. & Fang, M. Y. hTERT expression extends the life-span and maintains the cardiomyogenic potential of mesenchymal stem cells in human umbilical cord blood. Life Science Journal 8, 239\u2013243, https:\/\/doi.org\/10.7537\/marslsj080211.30 (2011).","journal-title":"Life Science Journal"},{"key":"47022_CR47","doi-asserted-by":"publisher","first-page":"4375","DOI":"10.1096\/fj.13-230904","volume":"27","author":"D Ding","year":"2013","unstructured":"Ding, D., Xi, P., Zhou, J., Wang, M. & Cong, Y. S. Human telomerase reverse transcriptase regulates MMP expression independently of telomerase activity via NF-kappaB-dependent transcription. FASEB J 27, 4375\u20134383, https:\/\/doi.org\/10.1096\/fj.13-230904 (2013).","journal-title":"FASEB J"},{"key":"47022_CR48","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/ncb2621","volume":"14","author":"A Ghosh","year":"2012","unstructured":"Ghosh, A. et al. Telomerase directly regulates NF-kappaB-dependent transcription. Nat Cell Biol 14, 1270\u20131281, https:\/\/doi.org\/10.1038\/ncb2621 (2012).","journal-title":"Nat Cell Biol"},{"key":"47022_CR49","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.cardfail.2017.03.002","volume":"23","author":"L Bao","year":"2017","unstructured":"Bao, L. et al. C-Kit Positive Cardiac Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells Synergistically Enhance Angiogenesis and Improve Cardiac Function After Myocardial Infarction in a Paracrine Manner. J Card Fail 23, 403\u2013415, https:\/\/doi.org\/10.1016\/j.cardfail.2017.03.002 (2017).","journal-title":"J Card Fail"},{"key":"47022_CR50","doi-asserted-by":"publisher","first-page":"e96725","DOI":"10.1371\/journal.pone.0096725","volume":"9","author":"KU Hong","year":"2014","unstructured":"Hong, K. U. et al. c-kit+ Cardiac stem cells alleviate post-myocardial infarction left ventricular dysfunction despite poor engraftment and negligible retention in the recipient heart. PLoS One 9, e96725, https:\/\/doi.org\/10.1371\/journal.pone.0096725 (2014).","journal-title":"PLoS One"},{"key":"47022_CR51","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","volume":"8","author":"WE Johnson","year":"2007","unstructured":"Johnson, W. E., Li, C. & Rabinovic, A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8, 118\u2013127, https:\/\/doi.org\/10.1093\/biostatistics\/kxj037 (2007).","journal-title":"Biostatistics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47022-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47022-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47022-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T11:43:38Z","timestamp":1671277418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-47022-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,22]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["47022"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-47022-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,22]]},"assertion":[{"value":"10 January 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10579"}}