A Tri‐Culture Heart‐on‐a‐Chip Platform With iPSC‐Derived Cardiac Cells for Predictive Cardiotoxicity Testing
Year: 2026
Type: article
Abstract: Drug development is hindered by high attrition rates, with clinical trial failures accounting for 90% of unsuccessful candidates and 60% of R&D costs, often due to unanticipated cardiotoxicity. Existing models lack physiological relevance, particularly the vascular component critical for drug distribution and cardioprotection. To address this, we developed a heart-on-a-chip (HoC) platform integrating human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, cardiac fibroblasts, and endothelial cells from a single cell line, ensuring genetic uniformity and native-like cell-cell interactions. The tri-culture system maintained >90% cell viability under perfusion for 7 days and exhibited functional maturity, as demonstrated by expected chronotropic responses to the β-agonist isoproterenol. Crucially, the inclusion of endothelial cells mitigated doxorubicin-induced cardiotoxicity, a protective effect absent in conventional models, highlighting the endothelial layer's role in replicating in vivo drug responses. By combining physiological mimicry with scalability, this HoC platform offers a transformative tool for improving preclinical cardiotoxicity assessment and reducing reliance on animal models.
Source: Advanced Healthcare Materials
Institutions: Institut d'Investigació Biomédica de Bellvitge, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Institut de Microelectrònica de Barcelona, Adam Mickiewicz University in Poznań, Institució Catalana de Recerca i Estudis Avançats, Universitat de Barcelona
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,880
Funders: Fundació la Marató de TV3, “la Caixa” Foundation, Centres de Recerca de Catalunya, Generalitat de Catalunya, Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya, Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Agència de Gestió d'Ajuts Universitaris i de Recerca, Agencia Estatal de Investigación, Direcció General de Recerca, Generalitat de Catalunya
Awards: G1039312466, G1175115578, G1568717892, G1715699596, G1936110492, G2038104832, G2064873908, G2262748287, G2462415295, G2640929160, G288263039, G294895050, G3005324705, G300979063, G3461529875, G3480869486, G3546882995, G3647239269, G4228227490, G425668148, G5080475149, G5852091828, G6656126374, G684631391, G7084143925, G7434936867, G7737363338, G787121397, G8522095481, G8893486244, G8970170367
OpenAlex ID: W7127434691