Cardiac hypertrophy is the abnormal enlargement or thickening of the heart muscle. This is caused by increases in cardiomyocyte size and changes in other heart muscle components such as the extracellular matrix. Interestingly, these changes can be physiological e.g., extreme exercise, or can be pathological e.g., hypertension, valve disease or drug- or chemical-induced toxicity.
3D cell-based models are ideal for detecting hypertrophy as changes in spheroid or microtissue size can be monitored over time. Our research at Cyprotex has evaluated human iPSC-derived cardiomyocytes in mono-culture or in tri-culture with cardiac fibroblasts and endothelial cells, to determine hypertrophy (spheroid/microtissue size and pro-BNP) and other structural cardiotoxic effects (calcium homeostasis, mitochondrial function and ATP content). The cells were chronically exposed over 14 days to a panel of 10 known hypertrophic agents, 4 other structural cardiotoxins and 2 compounds without any cardiotoxic effects.
Both mono- and tri-culture models exhibited spontaneous beating, a uniform size and shape and longevity ensuring that they were amenable to repeat dosing and monitoring over at least 14 days. The mono-culture model proved to be the most successful model for predicting hypertrophy based upon increases in microtissue size, however, both models were positive for the pro-BNP marker and able to detect structural cardiotoxins.
To learn more about our research, download the poster, which was presented at the SOT conference in Baltimore in March 2017.