{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:26:51Z","timestamp":1790972811656,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Children\u2019s Health Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The discovery of human pluripotent stem cells (hiPSCs) and advances in DNA editing techniques have opened opportunities for personalized cell-based therapies for a wide spectrum of diseases. It has gained importance as a valuable tool to investigate genetic and functional variations in congenital heart defects (CHDs), enabling the customization of treatment strategies. The ability to understand the disease process specific to the individual patient of interest provides this technology with a significant advantage over generic animal models. However, its utility as a disease-in-a-dish model requires identifying effective and efficient differentiation protocols that accurately reproduce disease traits. Currently, iPSC-related research relies heavily on the quality of cells and the properties of the differentiation technique In this review, we discuss the utility of iPSCs in bench CHD research, the molecular pathways involved in the differentiation of cardiomyocytes, and their applications in CHD disease modeling, therapeutics, and drug application.<\/jats:p>","DOI":"10.3390\/cells13171430","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T03:51:06Z","timestamp":1724730666000},"page":"1430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["iPSC-Derived Cardiomyocytes as a Disease Model to Understand the Biology of Congenital Heart Defects"],"prefix":"10.3390","volume":"13","author":[{"given":"Chithra K.","family":"Pushpan","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-7616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-4203","authenticated-orcid":false,"given":"Subramanyan Ram","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-7616, USA"},{"name":"Dr. C.C. and Mabel, L. Criss Heart Center, Children\u2019s Nebraska, 8200 Dodge St, Omaha, NE 68114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/sctm.20-0242","article-title":"Regulatory considerations for developing a phase I investigational new drug application for autologous induced pluripotent stem cells-based therapy product","volume":"10","author":"Jha","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Balafkan, N., Mostafavi, S., Schubert, M., Siller, R., Liang, K.X., Sullivan, G., and Bindoff, L.A. (2020). A method for differentiating human induced pluripotent stem cells toward functional cardiomyocytes in 96-well microplates. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73656-2"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ergir, E., Oliver-De la Cruz, J., Fernandes, S., Cassani, M., Niro, F., Pereira-Sousa, D., Vrbsky, J., Vinarsky, V., Perestrelo, A., and Debellis, D. (2022). Generation and Maturation of Human Ipsc-Derived 3d Organotypic Cardiac Microtissues in Long-Term Culture. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22225-w"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhu, K., Bao, X., Wang, Y., Lu, T., and Zhang, L. (2023). Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte modelling of cardiovascular diseases for natural compound discovery. Biomed. Pharmacother., 157.","DOI":"10.1016\/j.biopha.2022.113970"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Takahashi, F., Patel, P., Kitsuka, T., and Arai, K. (2023). The exciting realities and possibilities of ips-derived cardiomyocytes. Bioengineering, 10.","DOI":"10.3390\/bioengineering10020237"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1126\/science.1158799","article-title":"Induced pluripotent stem cells generated from patients with als can be differentiated into motor neurons","volume":"321","author":"Dimos","year":"2008","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.cell.2008.03.028","article-title":"Direct reprogramming of terminally differentiated mature b lymphocytes to pluripotency","volume":"133","author":"Hanna","year":"2008","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/cr.2011.107","article-title":"Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1","volume":"21","author":"Moon","year":"2011","journal-title":"Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nbt.1502","article-title":"Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2","volume":"26","author":"Huangfu","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1634\/stemcells.2008-0346","article-title":"Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts","volume":"26","author":"Mali","year":"2008","journal-title":"Stem Cells"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.stem.2008.10.004","article-title":"Induction of pluripotent stem cells from mouse embryonic fibroblasts by oct4 and klf4 with small-molecule Compounds","volume":"3","author":"Shi","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Singh, V.K., Kalsan, M., Kumar, N., Saini, A., and Chandra, R. (2015). Induced pluripotent stem cells: Applications in regenerative medicine, disease modeling, and drug discovery. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00002"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrg2937","article-title":"Methods for making induced pluripotent stem cells: Reprogramming \u00e0 la carte","volume":"12","author":"Belmonte","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1002\/cmdc.202100222","article-title":"Chalcone-Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering","volume":"16","author":"Raad","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1101\/gad.9.24.3027","article-title":"Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis","volume":"9","author":"Mishina","year":"1995","journal-title":"Genes Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1101\/gad.9.17.2105","article-title":"Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse","volume":"9","author":"Winnier","year":"1995","journal-title":"Genes Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/abbs\/gmy092","article-title":"TGF-\u03b2 Signaling in Cancer","volume":"50","author":"Gu","year":"2018","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1242\/dev.02322","article-title":"Isl1Cre reveals a common Bmp pathway in heart and limb development","volume":"133","author":"Yang","year":"2006","journal-title":"Development"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18531","DOI":"10.1073\/pnas.0703113104","article-title":"Distinct roles of Wnt\/\u03b2-catenin and Bmp signaling during early cardiogenesis","volume":"104","author":"Klaus","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.semcdb.2019.10.011","article-title":"Cardiac progenitors and paracrine mediators in cardiogenesis and heart regeneration","volume":"100","author":"Witman","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.celrep.2018.12.076","article-title":"TETs Regulate Proepicardial Cell Migration through Extracellular Matrix Organization during Zebrafish Cardiogenesis","volume":"26","author":"Lan","year":"2019","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13742","DOI":"10.1073\/pnas.1002077107","article-title":"Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells","volume":"107","author":"Evseenko","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1101\/gad.1279405","article-title":"Heart induction by Wnt antagonists depends on the homeodomain transcription factor Hex","volume":"19","author":"Foley","year":"2005","journal-title":"Genes Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.stem.2007.05.018","article-title":"The Renewal and Differentiation of Isl1+ Cardiovascular Progenitors Are Controlled by a Wnt\/\u03b2-Catenin Pathway","volume":"1","author":"Qyang","year":"2007","journal-title":"Cell Stem Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9319","DOI":"10.1073\/pnas.0701212104","article-title":"Canonical Wnt signaling functions in second heart field to promote right ventricular growth","volume":"104","author":"Ai","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mensah, I.K., Emerson, M.L., Tan, H.J., and Gowher, H. (2024). Cardiomyocyte Differentiation from mouse embryonic stem cells by wnt switch method. Cells, 13.","DOI":"10.3390\/cells13020132"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/dvdy.21502","article-title":"Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells","volume":"237","author":"Varadkar","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41569-018-0100-2","article-title":"Notch and interacting signalling pathways in cardiac development, disease, and regeneration","volume":"15","author":"MacGrogan","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/dvdy.21570","article-title":"Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway","volume":"237","author":"Sirbu","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Hsueh, Y.-C., Pratt, R.E., Dzau, V.J., and Hodgkinson, C.P. (2023). Novel method of differentiating human induced pluripotent stem cells to mature cardiomyocytes via Sfrp2. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-31144-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1161\/CIRCRESAHA.114.300522","article-title":"Cardiac Tissue Engineering: State of the Art","volume":"114","author":"Hirt","year":"2014","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41569-019-0331-x","article-title":"Cardiomyocyte maturation: Advances in knowledge and implications for regenerative medicine","volume":"17","author":"Karbassi","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1091\/mbc.e17-01-0014","article-title":"Mechanical regulation of cardiac fibroblast profibrotic phenotypes","volume":"28","author":"Herum","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/toxsci\/kfw069","article-title":"Cardiac non-myocyte cells show enhanced pharmacological function suggestive of contractile maturity in stem cell derived cardiomyocyte microtissues","volume":"152","author":"Ravenscroft","year":"2016","journal-title":"Toxicol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.stemcr.2019.08.013","article-title":"Fatty acids enhance the maturation of cardiomyocytes derived from human pluripotent stem cells","volume":"13","author":"Yang","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1186\/s13287-022-03209-z","article-title":"Small molecule-mediated rapid maturation of human induced pluripotent stem cell-derived cardiomyocytes","volume":"13","author":"Chirico","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Parrotta, E.I., Lucchino, V., Scaramuzzino, L., Scalise, S., and Cuda, G. (2020). Modeling cardiac disease mechanisms using induced pluripotent stem cell-derived cardiomyocytes: Progress, promises and challenges. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124354"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Grunert, M., Appelt, S., Sch\u00f6nhals, S., Mika, K., Cui, H., Cooper, A., Cyganek, L., Guan, K., and Sperling, S.R. (2020). Induced pluripotent stem cells of patients with Tetralogy of Fallot reveal transcriptional alterations in cardiomyocyte differentiation. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67872-z"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1161\/CIRCRESAHA.119.315653","article-title":"RNA sequencing analysis of induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients","volume":"126","author":"Kitani","year":"2020","journal-title":"Circ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e30123","DOI":"10.1097\/MD.0000000000030123","article-title":"Alternative splicing signatures of congenital heart disease and induced pluripotent stem cell-derived cardiomyocytes from congenital heart disease patients","volume":"101","author":"Xu","year":"2022","journal-title":"Medicine"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"416","DOI":"10.5966\/sctm.2013-0105","article-title":"An Induced pluripotent stem cell model of hypoplastic left heart syndrome (hlhs) reveals multiple expression and functional differences in hlhs-derived cardiac myocytes","volume":"3","author":"Jiang","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kim, M.-S., Fleres, B., Lovett, J., Anfinson, M., Samudrala, S.S.K., Kelly, L.J., Teigen, L.E., Cavanaugh, M., Marquez, M., and Geurts, A.M. (2020). Contractility of induced pluripotent stem cell-cardiomyocytes with an myh6 head domain variant associated with hypoplastic left heart syndrome. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00440"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.stem.2022.03.003","article-title":"Uncompensated mitochondrial oxidative stress underlies heart failure in an ipsc-derived model of congenital heart disease","volume":"29","author":"Xu","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_46","unstructured":"Diaz-Frias, J., and Guillaume, M. (2024). Tetralogy of Fallot, StatPearls Publishing."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s12041-020-01257-z","article-title":"Atypical microdeletion 22q11. 2 in a patient with tetralogy of fallot","volume":"100","author":"Carli","year":"2021","journal-title":"J. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1161\/CIRCRESAHA.118.313250","article-title":"Whole exome sequencing reveals the major genetic contributors to nonsyndromic tetralogy of fallot","volume":"124","author":"Page","year":"2019","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/hmg\/ddt400","article-title":"Tbx1 regulates brain vascularization","volume":"23","author":"Cioffi","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","first-page":"286","article-title":"Identification of the major genetic contributors to tetralogy of fallot","volume":"28","author":"Monaghan","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Harvey, D.C., Verma, R., Sedaghat, B., Hjelm, B.E., Morton, S.U., Seidman, J.G., and Kumar, S.R. (2023). Mutations in genes related to myocyte contraction and ventricular septum development in non-syndromic tetralogy of Fallot. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1249605"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.cardfail.2023.10.053","article-title":"Bicc1: A Potential biomarker for heart failure and cardio-renal syndrome","volume":"30","author":"Liu","year":"2024","journal-title":"J. Card. Fail."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/humu.21610","article-title":"Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia","volume":"33","author":"Kraus","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1161\/CIRCULATIONAHA.123.064213","article-title":"Abnormal progenitor cell differentiation and cardiomyocyte proliferation in hypoplastic right heart syndrome","volume":"149","author":"Yu","year":"2024","journal-title":"Circulation"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1161\/CIRCULATIONAHA.119.045317","article-title":"Patient-specific induced pluripotent stem cells implicate intrinsic impaired contractility in hypoplastic left heart syndrome","volume":"142","author":"Paige","year":"2020","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kobayashi, J., Yoshida, M., Tarui, S., Hirata, M., Nagai, Y., Kasahara, S., Naruse, K., Ito, H., Sano, S., and Oh, H. (2014). Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of nkx2\u20135, hand1, and notch1 in hypoplastic left heart syndrome. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102796"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e016528","DOI":"10.1161\/JAHA.120.016528","article-title":"Single-cell transcriptomics of engineered cardiac tissues from patient-specific induced pluripotent stem cell-derived cardiomyocytes reveals abnormal developmental trajectory and intrinsic contractile defects in hypoplastic right heart syndrome","volume":"9","author":"Lam","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1017\/erm.2022.43","article-title":"Precision medicine for long QT syndrome: Patient-specific iPSCs take the lead","volume":"25","author":"Yu","year":"2023","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0146-2806(97)80009-6","article-title":"The Long QT Syndrome","volume":"22","author":"Schwartz","year":"1997","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/heartjnl-2020-318259","article-title":"Diagnosis, management and therapeutic strategies for congenital long QT syndrome","volume":"108","author":"Wilde","year":"2021","journal-title":"Heart"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1161\/CIRCULATIONAHA.108.772053","article-title":"Congenital Long-QT Syndromes: Who\u2019s at risk 26?","volume":"117","author":"Berul","year":"2008","journal-title":"Circulation"},{"key":"ref_62","first-page":"143","article-title":"The long QT syndrome family of cardiac ion channelopathies: A HuGE review","volume":"8","author":"Modell","year":"2006","journal-title":"Anesth. Analg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1161\/01.CIR.102.10.1178","article-title":"Spectrum of mutations in Long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE","volume":"102","author":"Splawski","year":"2000","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.14797\/mdcj-10-1-29","article-title":"Genetics of long QT syndrome","volume":"10","author":"Tester","year":"2014","journal-title":"Methodist DeBakey Cardiovasc. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1093\/cvr\/cvy208","article-title":"Modelling inherited cardiac disease using human induced pluripotent stem cell-derived cardiomyocytes: Progress, pitfalls, and potential","volume":"114","author":"Balk","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1056\/NEJMoa0908679","article-title":"Patient-specific induced pluripotent stem-cell models for long-qt syndrome","volume":"363","author":"Moretti","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.3390\/cells11162495","article-title":"In vitro drug screening using ipsc-derived cardiomyocytes of a long qt-syndrome patient carrying kcnq1 & trpm4 dual mutation: An experimental personalized treatment","volume":"11","author":"Wang","year":"2022","journal-title":"Cells"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/cvr\/cvs206","article-title":"Disease characterization using LQTS-specific induced pluripotent stem cells","volume":"95","author":"Egashira","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrd.2016.245","article-title":"Induced pluripotent stem cell technology: A decade of progress","volume":"16","author":"Shi","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_70","first-page":"325","article-title":"Human iPSC-derived cardiomyocytes for investigation of disease mechanisms and therapeutic strategies in inherited arrhythmia syndromes: Strengths and limitations. Cardiovasc","volume":"31","author":"Casini","year":"2017","journal-title":"Drugs Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1101\/gad.349678.122","article-title":"Modeling congenital heart disease: Lessons from mice, hPSC-based models, and organoids","volume":"36","author":"Rao","year":"2022","journal-title":"Genes Dev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1093\/hmg\/ddx140","article-title":"Induced pluripotent stem cell modelling of HLHS underlines the contribution of dysfunctional NOTCH signalling to impaired cardiogenesis","volume":"26","author":"Yang","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.stem.2020.07.015","article-title":"Intrinsic endocardial defects contribute to hypoplastic left heart syndrome","volume":"27","author":"Miao","year":"2020","journal-title":"Cell Stem Cell"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/17\/1430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:05Z","timestamp":1760110985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/17\/1430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,26]]},"references-count":73,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cells13171430"],"URL":"https:\/\/doi.org\/10.3390\/cells13171430","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,26]]}}}