Abstract
Purpose of ReviewHuman cardiac tissue engineering holds great promise for early detection of drug-related cardiac toxicity and arrhythmogenicity during drug discovery and development. We describe shortcomings of the current drug development pathway, recent advances in the development of cardiac tissue constructs as drug testing platforms, and the challenges remaining in their widespread adoption.Recent FindingsHuman pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been used to develop a variety of constructs including cardiac spheroids, microtissues, strips, rings, and chambers. Several ambitious studies have used these constructs to test a significant number of drugs, and while most have shown proper negative inotropic and arrhythmogenic responses, few have been able to demonstrate positive inotropy, indicative of relative hPSC-CM immaturity.SummarySeveral engineered human cardiac tissue platforms have demonstrated native cardiac physiology and proper drug responses. Future studies addressing hPSC-CM immaturity and inclusion of patient-specific cell lines will further advance the utility of such models for in vitro drug development.
Highlights
The current drug development pathway is exorbitantly expensive and time-consuming
In order to increase the efficiency with which new drugs are discovered and brought to clinical trials, it is necessary to improve the human in vitro models used, to increase their biological relevance and enable the field to move away from a reliance on animal models as the gold standard
To address concerns of cardiac toxicity, great efforts have been put toward the development of engineered cardiac tissues from hPSC-CMs
Summary
The current drug development pathway is exorbitantly expensive and time-consuming. It is estimated that between 2009 and 2018, the median cost to bring a new drug to market was $985.3 million, including capitalized research and development investment costs [1]. Those on the smaller scale such as spheroids and microtissues more facilitate high-throughput cardiotoxicity screening while retaining some aspects of cardiac function, whereas larger platforms including cardiac sheets, strips, rings, and chambers are more suited to lower-throughput assessment of drug effect on cardiac function, as they more closely resemble native cardiac tissue and enable measurement of voltage propagation and force generation (Fig. 1).
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