{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:27:50Z","timestamp":1769117270764,"version":"3.49.0"},"reference-count":115,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-191855"],"award-info":[{"award-number":["PJT-191855"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Heart and Stroke Foundation of Canada","award":["G-24-0037532"],"award-info":[{"award-number":["G-24-0037532"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Atrial fibrillation (AF) is the most common sustained heart rhythm disorder. It is estimated that AF affects over 52 million people worldwide, with its prevalence expected to double in the next four decades. AF significantly increases the risk of stroke and heart failure, contributing to 340,000 excess deaths annually. Beyond these life-threatening complications, AF results in limitations in physical, emotional, and social well-being causing significant reductions in quality of life and resulting in 8.4 million disability-adjusted life-years per year, highlighting the wide-ranging impact of AF on public health. Moreover, AF is increasingly recognized for its association with cognitive decline and dementia. AF is a chronic and progressive disease characterized by rapid and erratic electrical activity in the atria, often in association with structural changes in the heart tissue. AF is often initiated by triggered activity, often from ectopic foci in the pulmonary veins. These triggered impulses may initiate AF via: (1) sustained rapid firing with secondary disorganization into fibrillatory waves, or (2) by triggering micro re-entrant circuits around the pulmonary venous-LA junction and within the atrial body. In each instance, AF perpetuation necessitates the presence of a vulnerable atrial substrate, which perpetuates and stabilizes re-entrant circuits through a combination of slowed and heterogeneous conduction, as well as functional conduction abnormalities (e.g., fibrosis disrupting tissue integrity, and abnormalities in the intercalated disks disrupting effective cell-to-cell coupling). The re-entry wavelength, determined by conduction velocity and refractory period, is shortened by slowed conduction, favoring AF maintenance. One major factor contributing to these changes is the disruption of the extracellular matrix (ECM), which is induced by atrial fibrosis. Fibrosis-driven disruption of the ECM, especially in the heart and blood vessels, is commonly caused by conditions such as aging, hypertension, diabetes, smoking, and chronic inflammatory or autoimmune diseases. These factors lead to excessive collagen and protein deposition by activated fibroblasts (i.e., myofibroblasts), resulting in increased tissue stiffness, maladaptive remodeling, and impaired organ function. Fibrosis typically occurs when cardiac fibroblasts are activated to myofibroblasts, resulting in the deposition of excessive collagen and other proteins. This change in ECM interferes with the normal electrical function of the heart by creating irregular, fibrotic regions. AF and atrial fibrosis have a reciprocal relationship: AF promotes fibrosis through fibroblast activation and extracellular matrix buildup, while atrial fibrosis can sustain and perpetuate AF, contributing to higher rates of AF recurrence after treatments such as catheter ablation or cardioversion.<\/jats:p>","DOI":"10.3390\/cells15020187","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:24:34Z","timestamp":1768901074000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Versatile hiPSC Models and Bioengineering Platforms for Investigation of Atrial Fibrosis and Fibrillation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7762-3957","authenticated-orcid":false,"given":"Behnam","family":"Panahi","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1593-0756","authenticated-orcid":false,"given":"Saif","family":"Dababneh","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Fadaei","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6079-8411","authenticated-orcid":false,"given":"Hosna","family":"Babini","sequence":"additional","affiliation":[{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjana","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maksymilian","family":"Prondzynski","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-6557","authenticated-orcid":false,"given":"Mohsen","family":"Akbari","sequence":"additional","affiliation":[{"name":"Laboratory for Innovations in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0497-776X","authenticated-orcid":false,"given":"Peter H.","family":"Backx","sequence":"additional","affiliation":[{"name":"Department of Biology, York University, 4700 Keele Street, Toronto, ON M3J 1P3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-5123","authenticated-orcid":false,"given":"Jason G.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montreal Heart Institute, Universit\u00e9 de Montr\u00e9al, Montreal, QC H1T 1C8, Canada"},{"name":"Center for Cardiovascular Innovation, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Rose","sequence":"additional","affiliation":[{"name":"Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, GAC66, Health Research Innovation Centre, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-3115","authenticated-orcid":false,"given":"Glen F.","family":"Tibbits","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"},{"name":"Cellular and Regenerative Medicine Centre, BC Children\u2019s Hospital Research Institute, Vancouver, BC V5Z 4H4, Canada"},{"name":"Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"},{"name":"Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eadg1222","DOI":"10.1126\/sciadv.adg1222","article-title":"Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation","volume":"10","author":"Brown","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, X., Li, Z., He, H., Wang, S., Su, H., and Kang, G. (2025). Global burden and health inequality of atrial fibrillation\/atrial flutter from 1990 to 2021. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1585980"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rush, K.L., Seaton, C.L., Burton, L., Loewen, P., O\u2019cOnnor, B.P., Moroz, L., Corman, K., Smith, M.A., and Andrade, J.G. (2023). Quality of life among patients with atrial fibrillation: A theoretically-guided cross-sectional study. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0291575"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41569-024-01088-w","article-title":"Translation of pathophysiological mechanisms of atrial fibrosis into new diagnostic and therapeutic approaches","volume":"22","author":"Schotten","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","unstructured":"Nesheiwat, Z., Goyal, A., and Jagtap, M. (2025). StatPearls, StatPearls Publishing LLC."},{"key":"ref_6","first-page":"e81264","article-title":"Causes, Diagnosis, Treatment, and Prognosis of Cardiac Fibrosis: A Systematic Review","volume":"17","author":"BaniHani","year":"2025","journal-title":"Cureus"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1093\/cvr\/cvab080","article-title":"New aspects of endocrine control of atrial fibrillation and possibilities for clinical translation","volume":"117","author":"Aguilar","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.hroo.2020.05.002","article-title":"Atrial remodeling and atrial fibrillation in acquired forms of cardiovascular disease","volume":"1","author":"Jansen","year":"2020","journal-title":"Heart Rhythm. O2"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Karakasis, P., Theofilis, P., Vlachakis, P.K., Korantzopoulos, P., Patoulias, D., Antoniadis, A.P., and Fragakis, N. (2024). Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010209"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/j.2040-4603.2015.tb00626.x","article-title":"Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions","volume":"Volume 5","author":"Pellman","year":"2015","journal-title":"Comprehensive Physiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2101636","DOI":"10.1002\/admt.202101636","article-title":"Latest Advances in 3D Bioprinting of Cardiac Tissues","volume":"7","author":"Jafari","year":"2022","journal-title":"Adv. Mater. Technol."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11886-021-01517-z","article-title":"Recent Advances in Single-Cell Profiling and Multispecific Therapeutics: Paving the Way for a New Era of Precision Medicine Targeting Cardiac Fibroblasts","volume":"23","author":"Shi","year":"2021","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1093\/eurheartj\/ehaf372","article-title":"Endothelial plasticity in atrial fibrosis by integrating single-cell sequencing and genetic lineage tracing","volume":"46","author":"Zeng","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1146\/annurev-physiol-021119-034527","article-title":"Cardiac Fibroblast Diversity","volume":"82","author":"Tallquist","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1161\/CIRCRESAHA.116.308139","article-title":"Recounting Cardiac Cellular Composition","volume":"118","author":"Zhou","year":"2017","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1161\/CIRCRESAHA.120.316958","article-title":"Myofibroblasts and Fibrosis: Mitochondrial and Metabolic Control of Cellular Differentiation","volume":"127","author":"Gibb","year":"2020","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1161\/01.CIR.0000102968.19341.FC","article-title":"Effect of Atrial Fibrillation on Hematopoietic Progenitor Cells","volume":"108","author":"Goette","year":"2003","journal-title":"Circulation"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1631\/jzus.B2300285","article-title":"Therapeutic advances in atrial fibrillation based on animal models","volume":"25","author":"Gong","year":"2024","journal-title":"J. Zhejiang Univ. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.120.316366","article-title":"Animal Models of Atrial Fibrillation","volume":"127","author":"Bapat","year":"2020","journal-title":"Circ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1091\/mbc.E16-01-0038","article-title":"Biology of the cardiac myocyte in heart disease","volume":"27","author":"Peter","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1093\/eurheartj\/ehae472","article-title":"Single-nucleus RNA sequencing identifies cell-type\u2013specific effects of sodium-glucose co-transporter 2 inhibitors in human myocardial slices","volume":"45","author":"Schmidt","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1093\/eurheartj\/ehae102","article-title":"Inhibition of miR-21: Cardioprotective effects in human failing myocardium ex vivo","volume":"45","author":"Abbas","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, T.-S., Lee, S.-T., Wawrowsky, K.A., Cheng, K., Galang, G., Malliaras, K., Roselle Abraham, M., Wang, C., and Marb\u00e1n, E. (2010). Dedifferentiation and Proliferation of Mammalian Cardiomyocytes. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012559"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Klumm, M.J., Heim, C., Fiegle, D.J., Weyand, M., Volk, T., and Seidel, T. (2022). Long-Term Cultivation of Human Atrial Myocardium. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.839139"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1089\/ten.teb.2021.0010","article-title":"Understanding Fibroblast Behavior in 3D Biomaterials","volume":"28","author":"Woodley","year":"2022","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1001\/jama.2022.8831","article-title":"Effect of MRI-Guided Fibrosis Ablation vs Conventional Catheter Ablation on Atrial Arrhythmia Recurrence in Patients with Persistent Atrial Fibrillation","volume":"327","author":"Marrouche","year":"2022","journal-title":"JAMA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.stemcr.2016.04.011","article-title":"Human Engineered Heart Tissue: Analysis of Contractile Force","volume":"7","author":"Mannhardt","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s44161-024-00489-x","article-title":"Assessing the arrhythmogenic propensity of fibrotic substrate using digital twins to inform a mechanisms-based atrial fibrillation ablation strategy","volume":"3","author":"Sakata","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41746-025-01625-y","article-title":"Digital twins enable stratification of persistent atrial fibrillation patients for ablation diminishing unnecessary heart damage","volume":"8","author":"Sakata","year":"2025","journal-title":"npj Digit. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.hrthm.2023.10.019","article-title":"Up digital and personal: How heart digital twins can transform heart patient care","volume":"21","author":"Trayanova","year":"2023","journal-title":"Heart Rhythm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1056\/NEJMoa2029980","article-title":"Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation","volume":"384","author":"Andrade","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.hroo.2025.02.007","article-title":"Clinical and socioeconomic factors associated with recurrent atrial fibrillation after catheter ablation or antiarrhythmic drug therapy","volume":"6","author":"An","year":"2025","journal-title":"Heart Rhythm. O2"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.hlc.2014.09.012","article-title":"Catheter Ablation of Atrial Fibrillation in Patients with Concomitant Left Ventricular Impairment: A Systematic Review of Efficacy and Effect on Ejection Fraction","volume":"24","author":"Ganesan","year":"2015","journal-title":"Heart Lung Circ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"euae104","DOI":"10.1093\/europace\/euae104","article-title":"Comprehensive atrial fibrillation burden and symptom reduction post-ablation: Insights from DECAAF II","volume":"26","author":"Noujaim","year":"2024","journal-title":"Europace"},{"key":"ref_36","first-page":"748","article-title":"Predicting recurrent atrial fibrillation after catheter ablation: A systematic review of prognostic models","volume":"22","author":"Dretzke","year":"2020","journal-title":"EP Eur."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102420","DOI":"10.1016\/j.scr.2021.102420","article-title":"Cardiac fibrosis models using human induced pluripotent stem cell-derived cardiac tissues allow anti-fibrotic drug screening in vitro","volume":"54","author":"Iseoka","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Cardona-Timoner, M., Gomes, R.N., and Nascimento, D.S. (2025). Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073038"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.stem.2020.05.004","article-title":"Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease","volume":"26","author":"Giacomelli","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7143","DOI":"10.1016\/j.cell.2024.09.034","article-title":"Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target","volume":"187","author":"Zhang","year":"2024","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.trsl.2024.07.003","article-title":"Fibrotic extracellular matrix impacts cardiomyocyte phenotype and function in an iPSC-derived isogenic model of cardiac fibrosis","volume":"273","author":"Niro","year":"2024","journal-title":"Transl. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Beauchamp, P., Jackson, C.B., Ozhathil, L.C., Agarkova, I., Galindo, C.L., Sawyer, D.B., Suter, T.M., and Zuppinger, C. (2020). 3D Co-culture of hiPSC-Derived Cardiomyocytes with Cardiac Fibroblasts Improves Tissue-Like Features of Cardiac Spheroids. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00014"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.stem.2017.07.003","article-title":"Human Pluripotent Stem Cell-Derived Atrial and Ventricular Cardiomyocytes Develop from Distinct Mesoderm Populations","volume":"21","author":"Lee","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/sctm.19-0440","article-title":"Drug screening platform using human induced pluripotent stem cell-derived atrial cardiomyocytes and optical mapping","volume":"10","author":"Gunawan","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s44325-024-00035-5","article-title":"Genetic and molecular underpinnings of atrial fibrillation","volume":"1","author":"Sweat","year":"2024","journal-title":"npj Cardiovasc. Health"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Babini, H., Jim\u00e9nez-S\u00e1bado, V., Stogova, E., Arslanova, A., Butt, M., Dababneh, S., Asghari, P., Moore, E.D.W., Claydon, T.W., and Chiamvimonvat, N. (2024). hiPSC-derived cardiomyocytes as a model to study the role of small-conductance Ca2+-activated K+ (SK) ion channel variants associated with atrial fibrillation. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1298007"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nagalingam, R.S., Jayousi, F., Hamledari, H., Dababneh, S., Hosseini, D., Lindsay, C., Geltink, R.K., Lange, P.F., Dixon, I.M., and Rose, R.A. (2024). Molecular and metabolomic characterization of hiPSC-derived cardiac fibroblasts transitioning to myofibroblasts. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1496884"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1161\/CIRCRESAHA.119.315491","article-title":"Generation of Quiescent Cardiac Fibroblasts From Human Induced Pluripotent Stem Cells for In Vitro Modeling of Cardiac Fibrosis","volume":"125","author":"Zhang","year":"2019","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.stem.2019.07.010","article-title":"Human Pluripotent Stem Cell-Derived Cardiovascular Cells: From Developmental Biology to Therapeutic Applications","volume":"25","author":"Protze","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.12688\/f1000research.139482.2","article-title":"Generation of a human iPSC-derived cardiomyocyte\/fibroblast engineered heart tissue model","volume":"12","author":"Cumberland","year":"2024","journal-title":"F1000Research"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"150038","DOI":"10.1098\/rsob.150038","article-title":"Crosstalk of cardiomyocytes and fibroblasts in co-cultures","volume":"5","author":"Rother","year":"2015","journal-title":"Open Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCRESAHA.117.305365","article-title":"Human Induced Pluripotent Stem Cell\u2013Derived Cardiomyocytes","volume":"117","author":"Karakikes","year":"2015","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3794","DOI":"10.1242\/jcs.029678","article-title":"Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: Scar-like rigidity inhibits beating","volume":"121","author":"Engler","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/ejhf.2631","article-title":"Accelerating cardiovascular research: Recent advances in translational 2D and 3D heart models","volume":"24","author":"Mohr","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1038\/s41467-024-50224-0","article-title":"Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems","volume":"15","author":"Prondzynski","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.cell.2018.11.042","article-title":"A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling","volume":"176","author":"Zhao","year":"2019","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1177\/2472555220975332","article-title":"A Scalable Approach Reveals Functional Responses of iPSC Cardiomyocyte 3D Spheroids","volume":"26","author":"Burnham","year":"2021","journal-title":"SLAS Discov. Adv. Sci. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/stcltm\/szae014","article-title":"Advances in 3D Bioprinted Cardiac Tissue Using Stem Cell-Derived Cardiomyocytes","volume":"13","author":"Bliley","year":"2024","journal-title":"Stem Cells Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26697","DOI":"10.31083\/RCM26697","article-title":"Advances and Prospects in Using Induced Pluripotent Stem Cells for 3D Bioprinting in Cardiac Tissue Engineering","volume":"26","author":"Du","year":"2025","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e2305911","DOI":"10.1002\/adma.202305911","article-title":"Direct 3D-Bioprinting of hiPSC-Derived Cardiomyocytes to Generate Functional Cardiac Tissues","volume":"35","author":"Esser","year":"2023","journal-title":"Adv. Mater."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s11886-023-01881-y","article-title":"3D Printing Approaches to Engineer Cardiac Tissue","volume":"25","author":"Lu","year":"2023","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2401528","DOI":"10.1002\/adma.202401528","article-title":"Embedding Biomimetic Vascular Networks via Coaxial Sacrificial Writing into Functional Tissue","volume":"36","author":"Stankey","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1900344","DOI":"10.1002\/advs.201900344","article-title":"3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts","volume":"6","author":"Noor","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1002\/term.2954","article-title":"Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo","volume":"13","author":"Yeung","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41586-018-0016-3","article-title":"Advanced maturation of human cardiac tissue grown from pluripotent stem cells","volume":"556","author":"Ma","year":"2018","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Liu, H., Fan, P., Jin, F., Huang, G., Guo, X., and Xu, F. (2022). Dynamic and static biomechanical traits of cardiac fibrosis. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1042030"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1021\/acsami.4c11934","article-title":"Cell Architecture and Dynamics of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hiPSC-CMs) on Hydrogels with Spatially Patterned Laminin and N-Cadherin","volume":"17","author":"Lane","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Schussler, O., Falcoz, P.E., Chachques, J.C., Alifano, M., and Lecarpentier, Y. (2021). Possible Treatment of Myocardial Infarct Based on Tissue Engineering Using a Cellularized Solid Collagen Scaffold Functionalized with Arg-Glyc-Asp (RGD) Peptide. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212563"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"17015","DOI":"10.1038\/s41598-024-67646-x","article-title":"3D matrix stiffness modulation unveils cardiac fibroblast phenotypic switching","volume":"14","author":"Han","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1161\/CIRCRESAHA.119.316155","article-title":"In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid","volume":"127","author":"Kupfer","year":"2020","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13532","DOI":"10.1038\/s41598-018-31848-x","article-title":"A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes","volume":"8","author":"Maiullari","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/s41598-017-01581-y","article-title":"Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers","volume":"7","author":"Dai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biomaterials.2016.09.003","article-title":"Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip","volume":"110","author":"Zhang","year":"2016","journal-title":"Biomaterials"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1038\/s41467-017-01946-x","article-title":"Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues","volume":"8","author":"Shadrin","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"394","DOI":"10.15252\/emmm.201404757","article-title":"Atrial-like cardiomyocytes from human pluripotent stem cells are a robust preclinical model for assessing atrial-selective pharmacology","volume":"7","author":"Devalla","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5268","DOI":"10.1038\/s41598-017-05652-y","article-title":"Modeling Atrial Fibrillation using Human Embryonic Stem Cell-Derived Atrial Tissue","volume":"7","author":"Laksman","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.actbio.2019.05.016","article-title":"Engineered heart tissue models from hiPSC-derived cardiomyocytes and cardiac ECM for disease modeling and drug testing applications","volume":"92","author":"Goldfracht","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1093\/intbio\/zyaa015","article-title":"Mechanical stretch sustains myofibroblast phenotype and function in microtissues through latent TGF-\u03b21 activation","volume":"12","author":"Walker","year":"2020","journal-title":"Integr. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"109869","DOI":"10.1016\/j.cellsig.2020.109869","article-title":"Diverse origins and activation of fibroblasts in cardiac fibrosis","volume":"78","author":"Aujla","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1089\/ten.tec.2017.0169","article-title":"Characterization and Standardization of Cultured Cardiac Fibroblasts for Ex Vivo Models of Heart Fibrosis and Heart Ischemia","volume":"23","author":"Zhou","year":"2017","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9363809","DOI":"10.1155\/2020\/9363809","article-title":"Human Cardiac Fibroblast Number and Activation State Modulate Electromechanical Function of hiPSC-Cardiomyocytes in Engineered Myocardium","volume":"2020","author":"Rupert","year":"2020","journal-title":"Stem Cells Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jshs.2022.12.011","article-title":"Beyond cardiomyocytes: Cellular diversity in the heart\u2019s response to exercise","volume":"12","author":"Trager","year":"2022","journal-title":"J. Sport Health Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1038\/s41467-019-09831-5","article-title":"Functional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"RP87739","DOI":"10.7554\/eLife.87739.3","article-title":"A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes","volume":"12","author":"Seguret","year":"2024","journal-title":"eLife"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Munawar, S., and Turnbull, I.C. (2021). Cardiac Tissue Engineering: Inclusion of Non-cardiomyocytes for Enhanced Features. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.653127"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"12137","DOI":"10.1038\/s41598-023-39369-y","article-title":"Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype","volume":"13","author":"Hall","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20417314251356321","article-title":"Cardiac fibroblast-mediated ECM remodeling regulates maturation in an in vitro 3D engineered cardiac tissue","volume":"16","author":"Jang","year":"2025","journal-title":"J. Tissue Eng."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1021\/acscentsci.9b00052","article-title":"Biowire Model of Interstitial and Focal Cardiac Fibrosis","volume":"5","author":"Wang","year":"2019","journal-title":"ACS Cent. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1007\/s11517-022-02648-3","article-title":"Atrial fibrosis identification with unipolar electrogram eigenvalue distribution analysis in multi-electrode arrays","volume":"60","author":"Riccio","year":"2022","journal-title":"Med. Biol. Eng. Comput."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e004412","DOI":"10.1161\/CIRCGEN.123.004412","article-title":"Atrial Fibrillation Related Titin Truncation Is Associated with Atrial Myopathy in Patient-Derived Induced Pluripotent Stem Cell Disease Models","volume":"18","author":"Huang","year":"2025","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e010077","DOI":"10.1161\/CIRCEP.121.010077","article-title":"Atrial Fibrillation in Aging and Frail Mice","volume":"14","author":"Jansen","year":"2021","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"H753","DOI":"10.1152\/ajpheart.00404.2012","article-title":"Processing and analysis of cardiac optical mapping data obtained with potentiometric dyes","volume":"303","author":"Laughner","year":"2012","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"euae017","DOI":"10.1093\/europace\/euae017","article-title":"Optical mapping and optogenetics in cardiac electrophysiology research and therapy: A state-of-the-art review","volume":"26","author":"Baines","year":"2024","journal-title":"Europace"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/j.hrthm.2016.03.019","article-title":"Percolation as a mechanism to explain atrial fractionated electrograms and reentry in a fibrosis model based on imaging data","volume":"13","author":"Vigmond","year":"2016","journal-title":"Heart Rhythm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e08","DOI":"10.15420\/aer.2021.52","article-title":"Future Directions for Mapping Atrial Fibrillation","volume":"11","author":"Zaman","year":"2022","journal-title":"Arrhythmia Electrophysiol. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"van Gorp, P.R.R., Trines, S.A., Pijnappels, D.A., and de Vries, A.A.F. (2020). Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00043"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1056\/NEJM199809033391003","article-title":"Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins","volume":"339","author":"Shah","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7996","DOI":"10.1038\/s41467-024-52221-9","article-title":"Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions","volume":"15","author":"Yang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/s41419-024-06703-9","article-title":"Modeling acute myocardial infarction and cardiac fibrosis using human induced pluripotent stem cell-derived multi-cellular heart organoids","volume":"15","author":"Song","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1093\/cvr\/cvad004","article-title":"Cardiac muscle patches containing four types of cardiac cells derived from human pluripotent stem cells improve recovery from cardiac injury in mice","volume":"119","author":"Lou","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"R\u00f8sand, \u00d8., Wang, J., Scrimgeour, N., Marwarha, G., and H\u00f8ydal, M.A. (2024). Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158460"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Xing, C., Bao, L., Li, W., and Fan, H. (2023). Progress on role of ion channels of cardiac fibroblasts in fibrosis. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1138306"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1161\/CIRCRESAHA.114.302226","article-title":"Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression","volume":"114","author":"Heijman","year":"2014","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Tani, H., and Tohyama, S. (2022). Human Engineered Heart Tissue Models for Disease Modeling and Drug Discovery. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.855763"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Scuderi, G.J., and Butcher, J. (2017). Naturally Engineered Maturation of Cardiomyocytes. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00050"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.stemcr.2018.10.008","article-title":"Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium","volume":"11","author":"Lemme","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.bbadis.2016.11.006","article-title":"The role of \u03b1-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling","volume":"1863","author":"Shinde","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"10160","DOI":"10.1038\/s41598-018-28393-y","article-title":"Characterization and Validation of a Human 3D Cardiac Microtissue for the Assessment of Changes in Cardiac Pathology","volume":"8","author":"Archer","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1038\/s41467-024-46928-y","article-title":"Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications","volume":"15","author":"Min","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e80479","DOI":"10.7554\/eLife.80479","article-title":"Single-cell RNA-seq of heart reveals intercellular communication drivers of myocardial fibrosis in diabetic cardiomyopathy","volume":"12","author":"Li","year":"2023","journal-title":"eLife"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1089\/scd.2019.0098","article-title":"Human Induced Pluripotent Stem Cell-Derived Non-Cardiomyocytes Modulate Cardiac Electrophysiological Maturation Through Connexin 43-Mediated Cell-Cell Interactions","volume":"29","author":"Clemens","year":"2020","journal-title":"Stem Cells Dev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"32","DOI":"10.5483\/BMBRep.2022-0185","article-title":"Engineered human cardiac tissues for modeling heart diseases","volume":"56","author":"Min","year":"2022","journal-title":"BMB Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.stem.2018.02.011","article-title":"Organs-on-a-Chip: A Fast Track for Engineered Human Tissues in Drug Development","volume":"22","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_114","first-page":"e133754","article-title":"Altered calcium handling produces reentry-promoting action potential alternans in atrial fibrillation\u2013remodeled hearts","volume":"5","author":"Liu","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_115","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"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/2\/187\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T05:25:06Z","timestamp":1769059506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/2\/187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":115,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["cells15020187"],"URL":"https:\/\/doi.org\/10.3390\/cells15020187","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}