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However, the efficacy of such treatments depends on the ability of transplanted cells to migrate and integrate into the damaged myocardium, a process that remains poorly understood. In this study, we investigated the migratory behaviour of hiPSC-CMs using homogenised rat MI tissue to simulate myocardial infarction (MI) in vitro. Transwell migration assays demonstrated a concentration-dependent chemotactic response, with hiPSC-CM migration increasing up to threefold towards MI tissue homogenate. Wound-healing assays further confirmed enhanced migration under MI-mimetic conditions. Bulk RNA sequencing revealed activation of the TGF-\u03b2 signalling pathway as a key regulator of this response. Inhibition of TGF-\u03b2 signalling, both pharmacologically and through antibody neutralisation, significantly reduced hiPSC-CM migration. These findings uncover a previously underappreciated chemotactic capability of hiPSC-CMs and identify TGF-\u03b2 signalling as a central mediator, offering new mechanistic insights and potential therapeutic targets to improve the integration and efficacy of hiPSC-CM-based cardiac regeneration strategies.<\/jats:p>","DOI":"10.1007\/s00395-026-01201-9","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T10:45:55Z","timestamp":1786531555000},"page":"1063-1076","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TGF-\u03b2 signalling drives chemotaxis of human induced pluripotent stem cell-derived cardiomyocytes in response to MI stimulus"],"prefix":"10.1007","volume":"121","author":[{"given":"Laura","family":"Deelen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowtham Reddy","family":"Cheruku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia Hafiz Abbas","family":"Gasim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-639X","authenticated-orcid":false,"given":"Fiona","family":"Lewis-McDougall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"1201_CR1","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1359-6101(03)00044-3","volume":"14","author":"M Azhar","year":"2003","unstructured":"Azhar M, Schultz JEJ, Grupp I, Dorn GW, Meneton P, Molin DGM, Gittenberger-de Groot AC, Doetschman T (2003) Transforming growth factor beta in cardiovascular development and function. 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