Abstract
Cardiotoxicity resulting from the side effects of the drugs leads to serious adverse events. Although drug efficacy and toxicity are primarily evaluated through animal testing, approximately 70% of drugs failed in phase II and phase III clinical trials due to the lack of efficacy and safety. These results indicated the insufficiency of current evaluation using animal models to accurately predict their efficacy and safety in human pathophysiology. Since the interspecies differences between human and animal models are one of the major reasons for these inadequate predictions of drug efficacy and toxicity in humans, in vitro engineered cardiac tissue (ECT) models using human-induced pluripotent stem cell-derived cardiomyoytes are expected to be in vitro platforms to evaluate the effect of the drugs on cardiac functions.
Poly (dimethylpolysiloxane) (PDMS) has been used as the material to implement ECTs on devices. However, the absorption of small molecules by PDMS is a serious issue that needs to be overcome. Here, we developed a low-absorption ECT device that is capable of analyzing contractile functions. Additionally, to avoid bias in the analysis, we generated a program to analyze contractile functions. Finally, we confirmed that this platform enabled the evaluation of the effect of small molecules on contractile functions.
Our findings suggest that our device could potentially improve the accuracy of drug evaluation by utilizing patient-derived human induced pluripotent stem cells and also contribute to a reduction in the number of animal tests.
