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bioRxiv · 10.1101/2025.06.06.658033

Stem cell-derived cardiomyocyte migration through TGF-β signalling in the context of myocardial infarction

Deelen, L.·Kobayashi, K.·Gasim, A. H. A.·Lewis-McDougall, F.·Suzuki, K.
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Abstract

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 toward MI tissue homogenate. Wound healing assays further confirmed enhanced migration under MI-mimetic conditions. Bulk RNA sequencing revealed activation of the TGF-{beta} signalling pathway as a key regulator of this response. Inhibition of TGF-{beta} 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-{beta} 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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Deelen, L., Kobayashi, K., Gasim, A. H. A., Lewis-McDougall, F., Suzuki, K.. 2025-06-08. Stem cell-derived cardiomyocyte migration through TGF-β signalling in the context of myocardial infarction. https://doi.org/10.1101/2025.06.06.658033

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