Key result
hiPSC-derived heart organoids demonstrated significant differences in cell viability and electrophysiology between breast cancer patients with and without doxorubicin-induced cardiotoxicity.
Why the study?
Heart organoid technology's ability to distinguish individual drug responses remained unclear, which is crucial for developing predictive models of doxorubicin-induced cardiotoxicity.
Patient-specific hiPSC-derived heart organoids can model individual differences in doxorubicin-induced cardiotoxicity, offering a potential platform for personalized drug response testing.
Patient-derived organoids may aid future cardiotoxicity risk stratification; hypothesis-generating and requires prospective clinical validation.
Heart organoid (HO) technology has successfully overcome the limitations of two-dimensional (2D) disease modeling and drug testing, thereby emerging as a valuable tool in drug discovery for assessing toxicity and efficacy. However, its ability to distinguish drug responses among individuals remain unclear, which is crucial for developing predictive models. We addressed this gap by comparing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with human induced pluripotent stem cell-derived heart organoids (hiPSC-HOs) in the context of doxorubicin-induced cardiotoxicity (DIC). For this study, we utilized hiPSCs generated from breast cancer patients who had previously been treated with doxorubicin. By comparing groups with and without DIC, we examined various parameters, including cell viability, mRNA expression, protein expression and electrophysiological variations. The results of our analysis revealed significant differences between these groups, providing insights into hiPSC-HOs as a potential platform for testing differences in drug responses among patients.
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Jang et al. (2024) studied Doxorubicin-induced cardiotoxicity. hiPSC-derived heart organoids (hiPSC-HOs) vs. hiPSC-derived cardiomyocytes (hiPSC-CMs) was evaluated on Cell viability, mRNA expression, protein expression and electrophysiological variations. hiPSC-derived heart organoids demonstrated significant differences in cell viability and electrophysiology between breast cancer patients with and without doxorubicin-induced cardiotoxicity.
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