{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:17:25Z","timestamp":1788329845252,"version":"build-2803163510"},"reference-count":82,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p xml:lang=\"en\">Cardiovascular disease remains the leading cause of global mortality, in part because the heart has limited regenerative capacity. Human\u2010induced pluripotent stem cells (hiPSCs) offer a scalable, patient\u2010specific platform for modeling heart disease, advancing drug discovery, and developing regenerative therapies. This review evaluates recent developments in hiPSC technology, beginning with the generation of patient\u2010specific models of inherited arrhythmias and cardiomyopathies. We examine progress in directing hiPSCs into specialized lineages, including cardiomyocytes, pacemaker cells, and Purkinje fibers, by highlighting key developmental signaling pathways and transcriptional regulators. Furthermore, we discuss emerging strategies for cell and therapeutic delivery, such as bioengineered patches and hydrogels, and address key challenges in cell maturation and functional integration. Finally, we review current clinical trials assessing the safety of hiPSC\u2010based treatments for heart failure and conduction disorders. These advancements underscore the dual potential of hiPSCs as essential research tools and as aspirational therapeutic resources.<\/jats:p>","DOI":"10.1161\/jaha.126.050981","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:42:53Z","timestamp":1787226173000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Stem Cell\u2010Derived Cardiac and Conduction System Cells for Heart Regeneration and Repair: Current Progress and Future Directions"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5382-0462","authenticated-orcid":false,"given":"Berra","family":"Koskulu","sequence":"first","affiliation":[{"name":"College of Pharmacy, University of Houston","place":["Houston, USA"]},{"name":"Cardiovascular Research Institute, Baylor College of Medicine","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7279-2514","authenticated-orcid":false,"given":"Tabish","family":"Ali","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4758-8622","authenticated-orcid":false,"given":"Ilkin","family":"Tetik\u2010Altintop","sequence":"additional","affiliation":[{"name":"College of Natural Science and Mathematics, University of Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleva","family":"Villanueva","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Houston","place":["Houston, USA"]},{"name":"Escuela Superior de Medicina\/Instituto Polit\u00e9cnico Nacional","place":["Ciudad de M\u00e9xico, M\u00e9xico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Gomola","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8712-0336","authenticated-orcid":false,"given":"Bradley K.","family":"McConnell","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Houston","place":["Houston, USA"]},{"name":"College of Natural Science and Mathematics, University of Houston","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1165-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063387"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13242045"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.024"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2016.12.002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.31083\/RCM28251"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11020334"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2018.11.015"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes16040419"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057329"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03172-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.156166"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01809-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124354"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131727"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01044-5"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1691-5"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00002"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58044-6"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20200833"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hg2103s87"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179155"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.302752"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.227405"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.159905"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55620-x"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/1535370217732737"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.581331"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes15060798"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31018"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-020-00470-2"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.09.014"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep31457"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1270951"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.06.009"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0168-1"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31706"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctdb.2016.08.008"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000215985.18538.c4"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2013-0110"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.187062"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3791\/52628"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.150"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200250109"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100334"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e10365"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.19-0440"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404757"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.163"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.31083\/j.rcm2508299"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.323180"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.09.015"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00618.2022"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3745"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.07.014"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01794-5"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2020.102043"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76781"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0681-4"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137318"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31161"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11738"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01942-w"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.22.614353"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105402"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052309"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-012-9378-3"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067097"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-021-00796-9"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy097"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2023.08.011"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-018-0229-7"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300556"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.01.083"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.2337\/db25-0204"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321951"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-025-01217-w"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.152756"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.08.003"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-056264"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2025.01.007"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.06.003"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.126.050981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:02:25Z","timestamp":1788328945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.126.050981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":82,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1161\/JAHA.126.050981"],"URL":"https:\/\/doi.org\/10.1161\/jaha.126.050981","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e050981"}}