iPSC-Derived Cardiomyocytes in Inherited Cardiac Arrhythmias: Pathomechanistic Discovery and Drug Development

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.

Automated summary

The discovery of induced pluripotent stem cells has allowed the generation of various cell types, including iPSC-derived cardiomyocytes, for different purposes such as disease modelling and drug discovery. While 2D iPSC-CM models have shown promise, they are less mature compared to adult cardiomyocytes. Novel approaches are being developed to create 3D models with added cell types, improving maturity and physiological relevance. This review focuses on the progress in modelling inherited cardiac arrhythmias using both 2D and 3D models, and their application in therapy development and drug testing.