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 |
Biosens Bioelectron
December 2024
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21205, United States; Department of Medicine, Johns Hopkins University, Baltimore, MD, 21205, United States; Institute for NanoBio Technology, Johns Hopkins University, Baltimore, MD, 21218, United States; Center for Microphysiological Systems, Johns Hopkins University, Baltimore, MD, 21205, United States. Electronic address:
Cardiotoxicity remains a major challenge in drug development, accounting for 45% of medication withdrawals due to cardiac ischemia and arrhythmogenicity. To overcome the limitations of traditional multielectrode array (MEA)-based cardiotoxicity assays, we developed a Nafion-coated NanoMEA platform with decoupled reference electrodes, offering enhanced sensitivity for electrophysiological measurements. The 'Decoupled' configuration significantly reduced polarization resistance (Rp) from 12.
View Article and Find Full Text PDFCells
December 2024
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control.
View Article and Find Full Text PDFThis study aimed to elucidate the impact of advanced glycation end products (AGEs) and glucose shock on cardiomyocyte viability, gene expression, cardiac biomarkers, and cardiac contractility. Firstly, AGEs were generated in-house, and their concentration was confirmed using absorbance measurements. AC16 cardiomyocytes were then exposed to varying doses of AGEs, resulting in dose-dependent decreases in cell viability.
View Article and Find Full Text PDFSci Data
December 2024
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Cardiac regenerative therapy has recently progressed by reprogramming somatic cells into induced pluripotent stem cells (iPSCs) and advanced by large-scale differentiation-derived cardiomyocytes (hiPSC-CMs). However, repairing damaged cardiac tissues with hiPSC-CMs remains limited due to immune rejection, cardiac arrhythmias, and concerns over tumor formation after hiPSC-CM transplantation. Despite efforts in profiling epigenomic changes during cardiac differentiation, regulatory mechanisms underlying 5-methylcytosine (mC) deposition in RNA mC epitranscriptomic landscape during hiPSC-to-cardiomyocyte differentiation remain unclear.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Federal Research Centre Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
The clinical significance of numerous cardiovascular gene variants remains to be determined. CRISPR/Cas9 allows for the introduction and/or correction of a certain variant in induced pluripotent stem cells (iPSCs). The resulting isogenic iPSC lines can be differentiated into cardiomyocytes and used as a platform to assess the pathogenicity of the variant.
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