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With the discovery of induced pluripotent stem cell (iPSCs) a wide range of cell types, including iPSC-derived cardiomyocytes (iPSC-CM), can now be generated from an unlimited source of somatic cells. These iPSC-CM are used for different purposes such as disease modelling, drug discovery, cardiotoxicity testing and personalised medicine. The 2D iPSC-CM models have shown promising results, but they are known to be more immature compared to in vivo adult cardiomyocytes. Novel approaches to create 3D models with the possible addition of other (cardiac) cell types are being developed. This will not only improve the maturity of the cells, but also leads to more physiologically relevant models that more closely resemble the human heart. In this review, we focus on the progress in the modelling of inherited cardiac arrhythmias in both 2D and 3D and on the use of these models in therapy development and drug testing.
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http://dx.doi.org/10.3390/biomedicines11020334 | DOI Listing |
Nat Cardiovasc Res
September 2025
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage.
View Article and Find Full Text PDFCancer cachexia is a highly debilitating clinical syndrome of involuntary body mass loss featuring profound muscle wasting leading to high mortality. Notably, cardiac wasting is prominent in cancer patients and cancer survivors. Cachexia studies present significant challenges due to the absence of human models and mainly short-term animal studies.
View Article and Find Full Text PDFFront Toxicol
August 2025
Ncardia Services B.V., Leiden, Netherlands.
Introduction: Efficient preclinical prediction of cardiovascular side effects poses a pivotal challenge for the pharmaceutical industry. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are becoming increasingly important in this field due to inaccessibility of human native cardiac tissue. Current preclinical hiPSC-CMs models focus on functional changes such as electrophysiological abnormalities, however other parameters, such as structural toxicity, remain less understood.
View Article and Find Full Text PDFRedox Biol
September 2025
National Clinical Research Center for Geriatric Diseases, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China; Institute of Geriatric Medicine, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China.
Small extracellular vesicles (sEVs) critically orchestrate inter-tissue and inter-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of doxorubicin-induced cardiotoxicity (DOXIC) via orchestrating the tumor cell-cardiomyocyte crosstalk has not yet been explored. Herein, we reveal that Doxorubicin (DOX)-treated breast cancer cells secrete sEVs (D-BCC-sEVs) that exacerbate DOX-induced ferroptosis of human iPSC-derived cardiomyocytes (hiCMs).
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2025
CERVO Brain Research Centre, Quebec City, QC, Canada; Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada. Electronic address:
Brugada syndrome is a rare inherited cardiac arrhythmia disorder primarily characterized by ventricular fibrillation, which can lead to sudden cardiac death. It follows an autosomal dominant pattern of inheritance and is most associated with dysfunction of the cardiac sodium channel Nav1.5.
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