Patient hiPSC-derived cardiomyocytes - "iPSC-derived cardiomyocytes as a model to dissect mechanical dysfunctions of caveolinopathies"
FLEXcyte 96 application note (2.6 MB)
patient hiPSC-derived cardiomyocytes
Cardiac diseases remain one of the major causes of mortality and morbidity in our society with enormous costs for the health system. Arrhythmias and cardiomyopathy diseases are difficult to prevent/cure because the molecular mechanisms behind their onset are in most cases not fully clarified. Causes and effect are often confused, even when directly studying patients’ cardiomyocytes, because of the maladaptive remodeling imposed by electro-mechanical alterations. To overcome this limitation, studying the arrhythmogenic risk associated with genetic cardiac diseases using patient-derived iPS-CMs, provides a good model.
Caveolinopathies are a group of muscular diseases that arise from mutation in the caveolin-3 gene (CAV3). Several CAV3 variants have been found in patients with both skeletal and cardiac pathologies. While electrophysiological alterations behind caveolinopathies have been partly elucidated using different models, the impact of such mutations on cardiomyocyte contraction and thus on the risk of developing cardiomyopathy, although quite probable, has never been studied before. Caveolin-3 along with cholesterol, forms membrane caveolae and plays a key role in the maintenance of plasma membrane integrity and interacts with several signaling proteins and ion channels.
Here, CardioExcyte 96 and FLEXcyte 96 compared relative amplitude and kinetics of contraction and relaxation in patient/control hiPS-lines in order to shed light on the relations between electrical and mechanical dysfunctions. This analysis offered various advantages, such as the possibility of electrical stimulation, recordings in an environment with an elastic surface area resembling that of the native cardiac tissue, as well as high throughput.