{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:05:24Z","timestamp":1780499124589,"version":"3.54.1"},"reference-count":161,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human adult cardiomyocytes (CMs) have limited regenerative capacity, posing a significant challenge in restoring cardiac function following substantial CM loss due to an acute ischemic event or chronic hemodynamic overload. Nearly half of patients show no improvement in left ventricular ejection fraction during recovery from acute myocardial infarction. At baseline, both humans and mice exhibit low but continuous cell turnover originating from the existing CMs. Moreover, myocardial infarction can induce endogenous CM cell cycling. Consequently, research has focused on identifying drivers of CM rejuvenation and proliferation from pre-existing CMs. High-throughput screening has facilitated the discovery of novel pro-proliferative targets through small molecules, microRNAs, and pathway-specific interventions. More recently, omics-based approaches such as single-nucleus RNA sequencing and spatial transcriptomics have expanded our understanding of cardiac cellular heterogeneity. The big-data strategies provide critical insights into why only a subset of CMs re-enter the cell cycle while most remain quiescent. In this review, we compare several high-throughput screening strategies used to identify novel targets for CM proliferation. We also summarize the benefits and limitations of various screening models\u2014including zebrafish embryos, rodent CMs, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and cardiac organoids\u2014underscoring the importance of integrating multiple systems to uncover new regenerative mechanisms. Further work is needed to identify translatable and safe targets capable of inducing functional CM expansion in clinical settings. By integrating high-throughput screening findings with insights into CM heterogeneity, this review provides a comprehensive framework for advancing cardiac regeneration research and guiding future therapeutic development.<\/jats:p>","DOI":"10.3390\/ijms27020601","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insights into Cardiomyocyte Regeneration from Screening and Transcriptomics Approaches"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5653-7849","authenticated-orcid":false,"given":"Daniela T.","family":"Fuller","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0428-9089","authenticated-orcid":false,"given":"Aaron H.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Michigan State University College of Human Medicine, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1986-6800","authenticated-orcid":false,"given":"Ruya","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1126\/science.1077857","article-title":"Heart regeneration in zebrafish","volume":"298","author":"Poss","year":"2002","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/978-1-4939-2495-0_18","article-title":"Assessing cardiomyocyte proliferative capacity in the newt heart and primary culture","volume":"Volume 1290","author":"Simon","year":"2015","journal-title":"Salamanders in Regeneration Research: Methods and Protocols; Methods in Molecular Biology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1126\/science.1200708","article-title":"Transient regenerative potential of the neonatal mouse heart","volume":"331","author":"Porrello","year":"2011","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1161\/CIRCULATIONAHA.117.030801","article-title":"Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration","volume":"137","author":"Natarajan","year":"2018","journal-title":"Circulation"},{"key":"ref_5","first-page":"H2183","article-title":"Cardiomyocyte DNA synthesis and binucleation during murine development","volume":"271","author":"Soonpaa","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.tig.2015.03.011","article-title":"When bigger is better: The role of polyploidy in organogenesis","volume":"31","year":"2015","journal-title":"Trends Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1089\/scd.2019.0193","article-title":"Residual Diploidy in Polyploid Tissues: A Cellular State with Enhanced Proliferative Capacity for Tissue Regeneration?","volume":"28","author":"Patterson","year":"2019","journal-title":"Stem Cells Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1038\/ng.3929","article-title":"Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration","volume":"49","author":"Patterson","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-physiol-021119-034618","article-title":"Cardiomyocyte Polyploidy and Implications for Heart Regeneration","volume":"82","author":"Gan","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1161\/CIRCULATIONAHA.119.045566","article-title":"Heart Regeneration by Endogenous Stem Cells and Cardiomyocyte Proliferation: Controversy, Fallacy, and Progress","volume":"142","author":"He","year":"2020","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17368","DOI":"10.3390\/ijms160817368","article-title":"Direct Reprogramming-The Future of Cardiac Regeneration?","volume":"16","author":"Doppler","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1126\/science.1164680","article-title":"Evidence for cardiomyocyte renewal in humans","volume":"324","author":"Bergmann","year":"2009","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature11682","article-title":"Mammalian heart renewal by pre-existing cardiomyocytes","volume":"493","author":"Senyo","year":"2013","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8850","DOI":"10.1073\/pnas.1408233111","article-title":"Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice","volume":"111","author":"Ali","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.cell.2015.05.026","article-title":"Dynamics of Cell Generation and Turnover in the Human Heart","volume":"161","author":"Bergmann","year":"2015","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1161\/CIRCRESAHA.120.318277","article-title":"Loss of Endogenously Cycling Adult Cardiomyocytes Worsens Myocardial Function","volume":"128","author":"Bradley","year":"2021","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1056\/NEJM200106073442303","article-title":"Evidence that human cardiac myocytes divide after myocardial infarction","volume":"344","author":"Beltrami","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/emmm.201201737","article-title":"Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart","volume":"5","author":"Malliaras","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1161\/CIRCULATIONAHA.123.067156","article-title":"A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease","volume":"151","author":"Derks","year":"2025","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1161\/CIRCULATIONAHA.116.024307","article-title":"Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury","volume":"136","author":"Wang","year":"2017","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/nature08804","article-title":"Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes","volume":"464","author":"Kikuchi","year":"2010","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8669","DOI":"10.1038\/s41598-021-88159-x","article-title":"GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration","volume":"11","author":"Fajardo","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s42255-020-0169-x","article-title":"Mitochondrial Substrate Utilization Regulates Cardiomyocyte Cell Cycle Progression","volume":"2","author":"Cardoso","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e50163","DOI":"10.7554\/eLife.50163","article-title":"Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart","volume":"8","author":"Honkoop","year":"2019","journal-title":"eLife"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1161\/CIRCRESAHA.119.315862","article-title":"Cardiomyocyte Maturation: New Phase in Development","volume":"126","author":"Guo","year":"2020","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Zhao, M.T., Ye, S., Su, J., and Garg, V. (2020). Cardiomyocyte Proliferation and Maturation: Two Sides of the Same Coin for Heart Regeneration. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.594226"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1161\/CIRCRESAHA.122.321770","article-title":"Proliferation and Maturation: Janus and the Art of Cardiac Tissue Engineering","volume":"132","author":"Singh","year":"2023","journal-title":"Circ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"BSR20200833","DOI":"10.1042\/BSR20200833","article-title":"Maturation strategies and limitations of induced pluripotent stem cell-derived cardiomyocytes","volume":"41","author":"Wu","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2741\/4581","article-title":"Differences in ion channel phenotype and function between humans and animal models","volume":"23","author":"Tanner","year":"2018","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1161\/CIRCULATIONAHA.108.808071","article-title":"Hemodynamic support by left ventricular assist devices reduces cardiomyocyte DNA content in the failing human heart","volume":"121","author":"Wohlschlaeger","year":"2010","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1161\/CIRCRESAHA.119.315408","article-title":"Polyploidy in Cardiomyocytes: Roadblock to Heart Regeneration?","volume":"126","author":"Derks","year":"2020","journal-title":"Circ. Res."},{"key":"ref_32","first-page":"e61866","article-title":"An Antegrade Perfusion Method for Cardiomyocyte Isolation from Mice","volume":"171","author":"Fukunaga","year":"2021","journal-title":"J. Vis. Exp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100950","DOI":"10.1016\/j.xpro.2021.100950","article-title":"Isolation, culture, and immunostaining of neonatal rat ventricular myocytes","volume":"2","author":"Pereira","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_34","first-page":"52726","article-title":"Isolation and cryopreservation of neonatal rat cardiomyocytes","volume":"98","author":"Vandergriff","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103461","DOI":"10.1016\/j.xpro.2024.103461","article-title":"Protocol for isolating and culturing neonatal murine cardiomyocytes","volume":"5","author":"Bongiovanni","year":"2024","journal-title":"STAR Protoc."},{"key":"ref_36","first-page":"e50154","article-title":"Isolation and culture of neonatal mouse cardiomyocytes","volume":"79","author":"Ehler","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/cr.2017.84","article-title":"Live cell screening platform identifies PPARdelta as a regulator of cardiomyocyte proliferation and cardiac repair","volume":"27","author":"Magadum","year":"2017","journal-title":"Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2007.12.033","article-title":"Visualizing spatiotemporal dynamics of multicellular cell-cycle progression","volume":"132","author":"Kurokawa","year":"2008","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.stem.2022.03.009","article-title":"A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration","volume":"29","author":"Du","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101903","DOI":"10.1016\/j.xpro.2022.101903","article-title":"Protocol to identify small molecules promoting rat and mouse cardiomyocyte proliferation based on the FUCCI and MADM reporters","volume":"3","author":"Zheng","year":"2022","journal-title":"STAR Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.cell.2005.02.012","article-title":"Mosaic analysis with double markers in mice","volume":"121","author":"Zong","year":"2005","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101560","DOI":"10.1016\/j.xpro.2022.101560","article-title":"A review of protocols for human iPSC culture, cardiac differentiation, subtype-specification, maturation, and direct reprogramming","volume":"3","author":"Wang","year":"2022","journal-title":"STAR Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.yjmcc.2018.12.015","article-title":"High-content phenotypic assay for proliferation of human iPSC-derived cardiomyocytes identifies L-type calcium channels as targets","volume":"127","author":"Woo","year":"2019","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cell.2018.02.014","article-title":"Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration","volume":"173","author":"Mohamed","year":"2018","journal-title":"Cell"},{"key":"ref_45","first-page":"H433","article-title":"Cardiac muscle tissue engineering: Toward an in vitro model for electrophysiological studies","volume":"277","author":"Bursac","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/(SICI)1097-0290(20000405)68:1<106::AID-BIT13>3.0.CO;2-3","article-title":"Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes","volume":"68","author":"Zimmermann","year":"2000","journal-title":"Biotechnol. Bioeng."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lewis-Israeli, Y.R., Wasserman, A.H., and Aguirre, A. (2021). Heart Organoids and Engineered Heart Tissues: Novel Tools for Modeling Human Cardiac Biology and Disease. Biomolecules, 11.","DOI":"10.3390\/biom11091277"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.semcdb.2021.03.011","article-title":"Heart organoids and tissue models for modeling development and disease","volume":"118","author":"Miyamoto","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.stem.2019.03.009","article-title":"Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-proliferative Compounds Acting via the Mevalonate Pathway","volume":"24","author":"Mills","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41536-025-00389-z","article-title":"Pharmacological or genetic inhibition of LTCC promotes cardiomyocyte proliferation through inhibition of calcineurin activity","volume":"10","author":"Devilee","year":"2025","journal-title":"npj Regen. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E8372","DOI":"10.1073\/pnas.1707316114","article-title":"Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest","volume":"114","author":"Mills","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eadu9375","DOI":"10.1126\/science.adu9375","article-title":"Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization","volume":"388","author":"Abilez","year":"2025","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kostina, A., Kiselev, A., Huang, A., Lankerd, H., Caywood, S., Jurado-Fernandez, A., Volmert, B., O\u2019Hern, C., Juhong, A., and Liu, Y. (2024). Self-organizing human heart assembloids with autologous and developmentally relevant cardiac neural crest-derived tissues. bioRxiv.","DOI":"10.2139\/ssrn.5063613"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.stem.2025.09.011","article-title":"Human heart-macrophage assembloids mimic immune-cardiac interactions and enable arrhythmia disease modeling","volume":"32","author":"Caywood","year":"2025","journal-title":"Cell Stem Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1016\/j.cell.2025.05.041","article-title":"Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids","volume":"188","author":"Miao","year":"2025","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1016\/j.stem.2021.11.007","article-title":"Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids","volume":"28","author":"Silva","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1038\/s41556-024-01526-4","article-title":"Blood-generating heart-forming organoids recapitulate co-development of the human haematopoietic system and the embryonic heart","volume":"26","author":"Dardano","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1038\/s41587-023-01718-7","article-title":"Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease","volume":"41","author":"Meier","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-neuro-111020-090812","article-title":"Challenges of Organoid Research","volume":"45","author":"Andrews","year":"2022","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1146\/annurev-genet-110711-155646","article-title":"Uncovering the molecular and cellular mechanisms of heart development using the zebrafish","volume":"46","author":"Staudt","year":"2012","journal-title":"Annu. Rev. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/wdev.37","article-title":"Small molecule screening in zebrafish: Swimming in potential drug therapies","volume":"1","author":"Tamplin","year":"2012","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.csbj.2016.09.001","article-title":"Zebrafish small molecule screens: Taking the phenotypic plunge","volume":"14","author":"Williams","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1242\/dev.088526","article-title":"In vivo monitoring of cardiomyocyte proliferation to identify chemical modifiers of heart regeneration","volume":"140","author":"Choi","year":"2013","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.devcel.2019.01.001","article-title":"Vitamin D Stimulates Cardiomyocyte Proliferation and Controls Organ Size and Regeneration in Zebrafish","volume":"48","author":"Han","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/j.chembiol.2011.09.015","article-title":"Discovering small molecules that promote cardiomyocyte generation by modulating Wnt signaling","volume":"18","author":"Ni","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1093\/jmcb\/mjz023","article-title":"Discovering small molecules as Wnt inhibitors that promote heart regeneration and injury repair","volume":"12","author":"Xie","year":"2020","journal-title":"J. Mol. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.devcel.2018.01.021","article-title":"Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish","volume":"44","author":"Sharpe","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Beffagna, G. (2019). Zebrafish as a Smart Model to Understand Regeneration After Heart Injury: How Fish Could Help Humans. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00107"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1039\/C8TX00261D","article-title":"A simple model to solve a complex drug toxicity problem","volume":"8","author":"Dixit","year":"2019","journal-title":"Toxicol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1021\/acs.jmedchem.1c01173","article-title":"High-Throughput Screening Platform in Postnatal Heart Cells and Chemical Probe Toolbox to Assess Cardiomyocyte Proliferation","volume":"65","author":"Becker","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/j.celrep.2018.04.049","article-title":"miRNAs that Induce Human Cardiomyocyte Proliferation Converge on the Hippo Pathway","volume":"23","author":"Wei","year":"2018","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"15917","DOI":"10.1038\/s41598-019-52467-0","article-title":"A simple and flexible high-throughput method for the study of cardiomyocyte proliferation","volume":"9","author":"Neininger","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1161\/CIRCGENETICS.113.000330","article-title":"Identification of chemicals inducing cardiomyocyte proliferation in developmental stage-specific manner with pluripotent stem cells","volume":"6","author":"Uosaki","year":"2013","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e128025","DOI":"10.1172\/jci.insight.128025","article-title":"The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice","volume":"4","author":"Yifa","year":"2019","journal-title":"JCI Insight"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbrc.2019.04.087","article-title":"Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts","volume":"513","author":"Haginiwa","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1101\/gad.1306705","article-title":"p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes","volume":"19","author":"Engel","year":"2005","journal-title":"Genes Dev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2668","DOI":"10.1161\/CIRCULATIONAHA.118.035832","article-title":"Long Noncoding RNA CPR (Cardiomyocyte Proliferation Regulator) Regulates Cardiomyocyte Proliferation and Cardiac Repair","volume":"139","author":"Ponnusamy","year":"2019","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cell.2009.04.060","article-title":"Neuregulin1\/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury","volume":"138","author":"Bersell","year":"2009","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.1038\/s41598-020-61491-4","article-title":"Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh(2) as an enhancer of skeletal and cardiac muscle regeneration","volume":"10","author":"Kim","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/s44161-022-00090-0","article-title":"Glucocorticoid receptor antagonization propels endogenous cardiomyocyte proliferation and cardiac regeneration","volume":"1","author":"Pianca","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"DEV204397","DOI":"10.1242\/dev.204397","article-title":"Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation","volume":"152","author":"Harris","year":"2025","journal-title":"Development"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/s44161-024-00450-y","article-title":"Identification of FDA-approved drugs that induce heart regeneration in mammals","volume":"3","author":"Ahmed","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e2414455","DOI":"10.1002\/advs.202414455","article-title":"Targeting miRNA-1a and miRNA-15b: A Novel Combinatorial Strategy to Drive Adult Cardiac Regeneration","volume":"12","author":"Yuan","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"251","DOI":"10.15252\/emmm.201606558","article-title":"Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration","volume":"9","author":"Cheng","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature11739","article-title":"Functional screening identifies miRNAs inducing cardiac regeneration","volume":"492","author":"Eulalio","year":"2012","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"106593","DOI":"10.1016\/j.isci.2023.106593","article-title":"Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation","volume":"26","author":"Renikunta","year":"2023","journal-title":"iScience"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Magadum, A., Renikunta, H.V., Singh, N., Estaras, C., Kishore, R., and Engel, F.B. (2022). Live cell screening identifies glycosides as enhancers of cardiomyocyte cell cycle activity. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.901396"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"24637","DOI":"10.1038\/srep24637","article-title":"Induction of Human iPSC-Derived Cardiomyocyte Proliferation Revealed by Combinatorial Screening in High Density Microbioreactor Arrays","volume":"6","author":"Titmarsh","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_89","first-page":"100295","article-title":"Matured hiPSC-derived cardiomyocytes possess dematuration plasticity","volume":"12","author":"Meng","year":"2025","journal-title":"J. Mol. Cell. Cardiol. Plus"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1007\/s12247-021-09587-w","article-title":"Cardiovascular Drugs: An Insight of In Silico Drug Design Tools","volume":"17","author":"Sarma","year":"2022","journal-title":"J. Pharm. Innov."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Tabana, Y., Babu, D., Fahlman, R., Siraki, A.G., and Barakat, K. (2023). Target identification of small molecules: An overview of the current applications in drug discovery. BMC Biotechnol., 23.","DOI":"10.1186\/s12896-023-00815-4"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"240167","DOI":"10.1098\/rsob.240167","article-title":"Cell cycle visualization tools to study cardiomyocyte proliferation in real-time","volume":"14","author":"Salmenov","year":"2024","journal-title":"Open Biol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Uosaki, H., Andersen, P., Shenje, L.T., Fernandez, L., Christiansen, S.L., and Kwon, C. (2012). Direct contact with endoderm-like cells efficiently induces cardiac progenitors from mouse and human pluripotent stem cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046413"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.yjmcc.2006.06.012","article-title":"Anillin localization defect in cardiomyocyte binucleation","volume":"41","author":"Engel","year":"2006","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1161\/CIRCRESAHA.118.312792","article-title":"Midbody Positioning and Distance Between Daughter Nuclei Enable Unequivocal Identification of Cardiomyocyte Cell Division in Mice","volume":"123","author":"Hesse","year":"2018","journal-title":"Circ. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1161\/CIRCRESAHA.118.313971","article-title":"Distinguishing Cardiomyocyte Division From Binucleation","volume":"123","author":"Kadow","year":"2018","journal-title":"Circ. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"sxaf018","DOI":"10.1093\/stmcls\/sxaf018","article-title":"Newborn apical resection preserves the proliferative capacity of cardiomyocytes located throughout the left ventricle","volume":"43","author":"Hao","year":"2025","journal-title":"Stem Cells"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1093\/cvr\/cvy056","article-title":"Cardiomyocyte binucleation is associated with aberrant mitotic microtubule distribution, mislocalization of RhoA and IQGAP3, as well as defective actomyosin ring anchorage and cleavage furrow ingression","volume":"114","author":"Leone","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e05563","DOI":"10.7554\/eLife.05563","article-title":"Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes","volume":"4","author":"Zebrowski","year":"2015","journal-title":"eLife"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.stemcr.2020.08.007","article-title":"Centrosome Reduction Promotes Terminal Differentiation of Human Cardiomyocytes","volume":"15","author":"Ng","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1161\/CIRCULATIONAHA.122.060985","article-title":"Impaired Reorganization of Centrosome Structure Underlies Human Infantile Dilated Cardiomyopathy","volume":"147","author":"Chun","year":"2023","journal-title":"Circulation"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"eabc4346","DOI":"10.1126\/science.abc4346","article-title":"Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair","volume":"371","author":"He","year":"2021","journal-title":"Science"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1038\/s41596-023-00833-8","article-title":"Genetic recording of in vivo cell proliferation by ProTracer","volume":"18","author":"Liu","year":"2023","journal-title":"Nat. Protoc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1038\/s41467-021-25933-5","article-title":"Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle","volume":"12","author":"Liu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Young, A., Bradley, L.A., and Wolf, M.J. (2022). In Vivo Methods to Monitor Cardiomyocyte Proliferation. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9030073"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1161\/CIRCRESAHA.122.320246","article-title":"Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction","volume":"130","author":"Pilz","year":"2022","journal-title":"Circ. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"dmm046565","DOI":"10.1242\/dmm.046565","article-title":"Mouse models of myocardial infarction: Comparing permanent ligation and ischaemia-reperfusion","volume":"13","author":"Riley","year":"2020","journal-title":"Dis. Models Mech."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/cbf.3587","article-title":"A review of myocardial ischaemia\/reperfusion injury: Pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment","volume":"39","author":"Gunata","year":"2021","journal-title":"Cell Biochem. Funct."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1093\/eurheartj\/ehab342","article-title":"Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: The ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology","volume":"42","author":"Zeymer","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ahj.2010.02.009","article-title":"Implications and reasons for the lack of use of reperfusion therapy in patients with ST-segment elevation myocardial infarction: Findings from the CRUSADE initiative","volume":"159","author":"Gharacholou","year":"2010","journal-title":"Am. Heart J."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e618","DOI":"10.1161\/CIR.0000000000000617","article-title":"Fourth Universal Definition of Myocardial Infarction (2018)","volume":"138","author":"Thygesen","year":"2018","journal-title":"Circulation"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s13287-019-1271-4","article-title":"Human embryonic stem cell-derived cardiomyocyte therapy in mouse permanent ischemia and ischemia-reperfusion models","volume":"10","author":"Yu","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"13839","DOI":"10.1073\/pnas.1313192110","article-title":"Hippo pathway effector Yap promotes cardiac regeneration","volume":"110","author":"Xin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"eabd6892","DOI":"10.1126\/scitranslmed.abd6892","article-title":"Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction","volume":"13","author":"Liu","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1161\/CIRCRESAHA.123.322929","article-title":"CCND2 Modified mRNA Activates Cell Cycle of Cardiomyocytes in Hearts With Myocardial Infarction in Mice and Pigs","volume":"133","author":"Sun","year":"2023","journal-title":"Circ. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/s41586-019-1191-6","article-title":"MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs","volume":"569","author":"Gabisonia","year":"2019","journal-title":"Nature"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1038\/s41467-021-25211-4","article-title":"A microRNA program regulates the balance between cardiomyocyte hyperplasia and hypertrophy and stimulates cardiac regeneration","volume":"12","author":"Raso","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s42003-025-08012-z","article-title":"Intronic RNAscope probes enable precise identification of cardiomyocyte nuclei and cell cycle activity","volume":"8","author":"Yu","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"109391","DOI":"10.1016\/j.biopha.2019.109391","article-title":"Effects of hypoxia on cardiomyocyte proliferation and association with stage of development","volume":"118","author":"Sun","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/s44161-022-00160-3","article-title":"Single-cell and spatial transcriptomics of the infarcted heart define the dynamic onset of the border zone in response to mechanical destabilization","volume":"1","author":"Calcagno","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"eadt9446","DOI":"10.1126\/sciadv.adt9446","article-title":"PTMA controls cardiomyocyte proliferation and cardiac repair by enhancing STAT3 acetylation","volume":"11","author":"Liu","year":"2025","journal-title":"Sci. Adv."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.devcel.2020.02.019","article-title":"Dynamic Transcriptional Responses to Injury of Regenerative and Non-regenerative Cardiomyocytes Revealed by Single-Nucleus RNA Sequencing","volume":"53","author":"Cui","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Wang, H., Dong, Y., Song, Y., Colon, M., Yapundich, N., Ricketts, S., Liu, X., Farber, G., Qian, Y., and Qian, L. (2025). Charting Postnatal Heart Development Using In Vivo Single-Cell Functional Genomics. bioRxiv.","DOI":"10.1101\/2025.03.10.642473"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1161\/CIRCULATIONAHA.121.056995","article-title":"Single Nucleus Transcriptomics: Apical Resection in Newborn Pigs Extends the Time Window of Cardiomyocyte Proliferation and Myocardial Regeneration","volume":"145","author":"Nakada","year":"2022","journal-title":"Circulation"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Copeland, K.M., Brazile, B.L., Butler, J.R., Cooley, J., Brinkman-Ferguson, E., Claude, A., Lin, S., Rais-Rohani, S., Welch, B., and McMahan, S.R. (2022). Investigating the Transient Regenerative Potential of Cardiac Muscle Using a Neonatal Pig Partial Apical Resection Model. Bioengineering, 9.","DOI":"10.3390\/bioengineering9080401"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Ellman, D.G., Slaiman, I.M., Mathiesen, S.B., Andersen, K.S., Hofmeister, W., Ober, E.A., and Andersen, D.C. (2021). Apex Resection in Zebrafish (Danio rerio) as a Model of Heart Regeneration: A Video-Assisted Guide. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115865"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Galow, A.M., Wolfien, M., Muller, P., Bartsch, M., Brunner, R.M., Hoeflich, A., Wolkenhauer, O., David, R., and Goldammer, T. (2020). Integrative Cluster Analysis of Whole Hearts Reveals Proliferative Cardiomyocytes in Adult Mice. Cells, 9.","DOI":"10.3390\/cells9051144"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41421-019-0095-9","article-title":"Single-cell imaging and transcriptomic analyses of endogenous cardiomyocyte dedifferentiation and cycling","volume":"5","author":"Zhang","year":"2019","journal-title":"Cell Discov."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/s44161-022-00028-6","article-title":"Single-cell transcriptomics reveals cell-type-specific diversification in human heart failure","volume":"1","author":"Koenig","year":"2022","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1161\/CIRCULATIONAHA.123.066004","article-title":"YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division","volume":"151","author":"Morikawa","year":"2025","journal-title":"Circulation"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s44161-024-00588-9","article-title":"Cross-species comparison reveals that Hmga1 reduces H3K27me3 levels to promote cardiomyocyte proliferation and cardiac regeneration","volume":"4","author":"Bouwman","year":"2025","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nature24045","article-title":"Hippo pathway deficiency reverses systolic heart failure after infarction","volume":"550","author":"Leach","year":"2017","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1161\/CIRCULATIONAHA.115.019357","article-title":"Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction","volume":"133","author":"Xiang","year":"2016","journal-title":"Circulation"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1161\/CIRCRESAHA.115.303632","article-title":"Cardiac-specific YAP activation improves cardiac function and survival in an experimental murine MI model","volume":"115","author":"Lin","year":"2014","journal-title":"Circ. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41536-023-00282-7","article-title":"Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration","volume":"8","author":"Tan","year":"2023","journal-title":"npj Regen. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.7150\/thno.32734","article-title":"Regulatory T-cells regulate neonatal heart regeneration by potentiating cardiomyocyte proliferation in a paracrine manner","volume":"9","author":"Li","year":"2019","journal-title":"Theranostics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"108472","DOI":"10.1016\/j.celrep.2020.108472","article-title":"Cell-Type-Specific Gene Regulatory Networks Underlying Murine Neonatal Heart Regeneration at Single-Cell Resolution","volume":"33","author":"Wang","year":"2020","journal-title":"Cell Rep."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e84679","DOI":"10.7554\/eLife.84679","article-title":"Comparative single-cell profiling reveals distinct cardiac resident macrophages essential for zebrafish heart regeneration","volume":"12","author":"Wei","year":"2023","journal-title":"eLife"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1038\/s41467-025-59169-4","article-title":"Border-zone cardiomyocytes and macrophages regulate extracellular matrix remodeling to promote cardiomyocyte protrusion during cardiac regeneration","volume":"16","author":"Constanty","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1161\/CIRCULATIONAHA.123.066298","article-title":"Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair","volume":"149","author":"Feng","year":"2024","journal-title":"Circulation"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1038\/s41467-020-16204-w","article-title":"Single-cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation","volume":"11","author":"Wang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.phrs.2017.07.020","article-title":"The epicardium as a source of multipotent adult cardiac progenitor cells: Their origin, role and fate","volume":"127","author":"Smits","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41556-022-00902-2","article-title":"Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders","volume":"24","author":"Eroglu","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.yjmcc.2011.08.020","article-title":"Thymosin beta 4 treatment after myocardial infarction does not reprogram epicardial cells into cardiomyocytes","volume":"52","author":"Zhou","year":"2012","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/CIRCULATIONAHA.121.055468","article-title":"hapln1 Defines an Epicardial Cell Subpopulation Required for Cardiomyocyte Expansion During Heart Morphogenesis and Regeneration","volume":"146","author":"Sun","year":"2022","journal-title":"Circulation"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41536-024-00378-8","article-title":"Heart regeneration from the whole-organism perspective to single-cell resolution","volume":"9","author":"Chen","year":"2024","journal-title":"npj Regen. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"eadk4694","DOI":"10.1126\/sciadv.adk4694","article-title":"Single-cell chromatin profiling reveals genetic programs activating proregenerative states in nonmyocyte cells","volume":"10","author":"Dong","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.yjmcc.2021.09.002","article-title":"Delineating chromatin accessibility re-patterning at single cell level during early stage of direct cardiac reprogramming","volume":"162","author":"Wang","year":"2022","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41569-020-00499-9","article-title":"Targeted delivery of therapeutic agents to the heart","volume":"18","author":"Sahoo","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Vekstein, A.M., Wendell, D.C., DeLuca, S., Yan, R., Chen, Y., Bishawi, M., Devlin, G.W., Asokan, A., Poss, K.D., and Bowles, D.E. (2022). Targeted Delivery for Cardiac Regeneration: Comparison of Intra-coronary Infusion and Intra-myocardial Injection in Porcine Hearts. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.833335"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2594555","DOI":"10.1080\/10717544.2025.2594555","article-title":"Breakthroughs of ultrasound-targeted microbubble destruction in treating myocardial ischemia-reperfusion injury: From angiogenesis regulation to precise inflammation suppression","volume":"32","author":"Feng","year":"2025","journal-title":"Drug Deliv."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.ymthe.2020.11.010","article-title":"In Vivo Validation of a Reversible Small Molecule-Based Switch for Synthetic Self-Amplifying mRNA Regulation","volume":"29","author":"Kitada","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1039\/C5CS00798D","article-title":"Smart micro\/nanoparticles in stimulus-responsive drug\/gene delivery systems","volume":"45","author":"Karimi","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1172\/JCI81870","article-title":"Cardiomyocyte proliferation prevents failure in pressure overload but not volume overload","volume":"127","author":"Toischer","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1126\/science.1199010","article-title":"Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size","volume":"332","author":"Heallen","year":"2011","journal-title":"Science"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11936-025-01107-0","article-title":"Advances in Drug Discovery for Cardiomyocyte Proliferation","volume":"27","author":"Wintruba","year":"2025","journal-title":"Curr. Treat. Options Cardiovasc. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41536-025-00394-2","article-title":"Revitalizing the heart: Strategies and tools for cardiomyocyte regeneration post-myocardial infarction","volume":"10","author":"Bois","year":"2025","journal-title":"npj Regen. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jacbts.2024.12.014","article-title":"Delayed miR-199a Administration After Myocardial Infarction Precludes Pro-Regenerative Effects","volume":"10","author":"Burjanadze","year":"2025","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"e132796","DOI":"10.1172\/jci.insight.132796","article-title":"Myocardial protection by nanomaterials formulated with CHIR99021 and FGF1","volume":"5","author":"Fan","year":"2020","journal-title":"JCI Insight"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"eaaw6419","DOI":"10.1126\/scitranslmed.aaw6419","article-title":"Control of cytokinesis by beta-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment","volume":"11","author":"Liu","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ijcard.2021.07.020","article-title":"Design and rationale of a clinical trial to increase cardiomyocyte division in infants with tetralogy of Fallot","volume":"339","author":"Fabio","year":"2021","journal-title":"Int. J. 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