Cardiac Structural Anomalies and Repair
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A previously underappreciated chemotactic capability of hiPSC-CMs is uncovered and TGF-β signalling is identified as a central mediator of this response, offering new mechanistic insights and potential therapeutic targets to improve the integration and efficacy of hiPSC-CM-based cardiac regeneration strategies.
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Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold significant promise for cardiac regeneration therapies. 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-β signalling pathway as a key regulator of this response. Inhibition of TGF-β 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-β 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.
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@article{Deelen2026signalling,
title = {TGF-β signalling drives chemotaxis of human induced pluripotent stem cell-derived cardiomyocytes in response to MI stimulus},
author = {Laura Deelen and Kazuya Kobayashi and Gowtham Reddy Cheruku and Alia Hafiz Abbas Gasim and Fiona Lewis and Ken Suzuki},
journal = {Basic Research in Cardiology},
year = {2026},
doi = {10.1007/s00395-026-01201-9},
url = {https://doi.org/10.1007/s00395-026-01201-9}
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