{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:13:23Z","timestamp":1790392403094,"version":"4.1.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMw Open"},{"name":"Competition"},{"name":"CONTRACT","award":["09120012010018"],"award-info":[{"award-number":["09120012010018"]}]},{"DOI":"10.13039\/100018890","name":"Dutch CardioVascular Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018890","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Double-Dose","award":["2020B005"],"award-info":[{"award-number":["2020B005"]}]},{"DOI":"10.13039\/501100020407","name":"ERA-CVD","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020407","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SCALE","award":["2019T109"],"award-info":[{"award-number":["2019T109"]}]},{"name":"Leducq"},{"name":"PRIORITY","award":["24CVD03"],"award-info":[{"award-number":["24CVD03"]}]},{"name":"EU Horizon"},{"DOI":"10.13039\/501100024951","name":"IMPACT","doi-asserted-by":"publisher","award":["101115536"],"award-info":[{"award-number":["101115536"]}],"id":[{"id":"10.13039\/501100024951","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In vitro gene editing using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has demonstrated the feasibility of introducing or correcting specific pathogenic variants. These successes represent a key first step towards therapeutic genome editing for cardiomyopathies, showing that precise, variant-specific interventions are achievable. To translate in vitro findings to the clinic, it is essential to develop robust disease models that yield meaningful, translatable data. The next challenge is systematically identifying disease-causing variants amenable to gene editing with strong pre-clinical support. Therefore, we conducted a systematic search of published studies on isogenic hiPSC-CM pairs in cardiomyopathy research with specific criteria, including (likely) pathogenic variants causing cardiomyopathy, correction and\/or introduction of variants, differentiation into CMs, and functional follow-up. We systematically assessed 785 papers and highlighted 101 studies meeting our inclusion criteria reporting 69 patients carrying 56 unique variants across 31 genes, most commonly MYH7, MYBPC3, and DMD. This expanded to 91 variants across 38 genes upon inclusion of the introduced variants in a donor line. However, reported clinical data were often incomplete, underscoring the need for standardized phenotypic documentation. We reveal a lack of patient details, which creates an incomplete picture of underlying disease variables that hinder the design of targeted personalized treatments. Omitted key clinical data can lead to misinterpretations or overlooked variables that impact treatment outcomes. This systematic review integrates current evidence from successful in vitro studies using isogenic hiPSC-CM models and proposes a reporting framework for variant prioritization and the rigorous application of isogenic controls in cardiomyopathy research.<\/jats:p>","DOI":"10.1093\/ehjopen\/oeaf161","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:53:55Z","timestamp":1764680035000},"source":"Crossref","is-referenced-by-count":2,"title":["Setting the stage for cardiomyopathy gene editing trials: a systematic review of isogenic pair use in human induced pluripotent stem cell-derived cardiomyocyte research"],"prefix":"10.1093","volume":"6","author":[{"given":"C Nina","family":"van der Wilt","sequence":"first","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier J A","family":"Veltrop","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]},{"name":"Department of Biochemistry, CARIM, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,","place":["The Netherlands"]},{"name":"LMNAcardiac.org, LMNA Patient Organization , Vredehofstraat 13761, HA Soest ,","place":["The Netherlands"]},{"name":"Netherlands Heart Institute, Holland Heart House , Moreelsepark 1, 3511 EP Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike H","family":"Janssens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iara","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Stillitano","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]},{"name":"Netherlands Heart Institute, Holland Heart House , Moreelsepark 1, 3511 EP Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost P G","family":"Sluijter","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-0661","authenticated-orcid":false,"given":"Linda W","family":"van Laake","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-5788","authenticated-orcid":false,"given":"Jolanda","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center , De Boelelaan 1108, 1081 HZ Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Villard","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMRS 1166 , 47-83, Boulevard de l'H\u00f4pital, 75013 Paris ,","place":["France"]},{"name":"APHP, Piti\u00e9-Salp\u00eatri\u00e8re University Hospital , 47-83 Boulevard de l'H\u00f4pital, 75013 Paris ,","place":["France"]},{"name":"ICAN Biocell iPS Core \u2013 Institute for Cardiometabolism and Nutrition , 47-83 Boulevard de l'H\u00f4pital, 75013 Paris 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Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4694-4790","authenticated-orcid":false,"given":"Anneline S J M","family":"te Riele","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-686X","authenticated-orcid":false,"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon J","family":"Schurgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, CARIM, Maastricht University , Universiteitssingel 50, 6229 ER Maastricht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G","family":"van Steenbeek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University , Heidelberglaan 100, 3584 CX Utrecht ,","place":["The Netherlands"]},{"name":"Regenerative Medicine Center Utrecht and Circulatory Health Research Center, University Medical Center Utrecht, Utrecht University , Heidelberglaan 8, 3584 CS Utrecht ,","place":["The Netherlands"]},{"name":"Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University , Yalelaan 104-106, 3584 CM Utrecht ,","place":["The 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