Abstract
In recent years, the cost of drug discovery and development have been progressively increasing, but the number of drugs approved for treatment of cardiovascular diseases (CVDs) has been limited. Current in vitro models for drug development do not sufficiently ensure safety and efficacy, owing to their lack of physiological relevance. On the other hand, preclinical animal models are extremely costly and present problems of inaccuracy due to species differences. To address these limitations, tissue chips offer the opportunity to emulate physiological and pathological tissue processes in a biomimetic in vitro platform. Tissue chips enable in vitro modeling of CVDs to give mechanistic insights, and they can also be a powerful approach for drug screening applications. Here, we review recent advances in CVD modeling using tissue chips and their applications in drug screening.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide (Virani Salim et al, 2020)
In a list of Food and Drug Administration (FDA) approved drugs in 2020, there were no new drug approved for the treatment of CVD, which encompass more than half of all CVDs (U.S Food and Drug Administraion (FDA), 2020)
Using a mixture of human induced pluripotent stem cells (iPSC)-derived CMs and non-myocytes to make up tissue sheets of 5–6 cell layers, it was shown that cell heterogeneity was key in recapitulating torsade de pointes arrhythmia (Kawatou et al, 2017)
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide (Virani Salim et al, 2020). Current methods of cardiotoxicity screening in vitro rely heavily on the use of cell lines that express cardiac specific ion channels, whereby the drugs interactions with the ion channels are directly observed for evaluation. Following these in vitro assays, drug candidates undergo further cardiotoxicity testing in vivo before entering clinical trials. Cardiovascular tissue chips can complement the current developmental pipeline for drug discovery. In this focused review, we will describe the various strategies by which cardiovascular tissue chips have been developed for disease modeling or drug screening applications, and discuss emerging areas in this field
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