A Change of Heart: Human Cardiac Tissue Engineering as a Platform for Drug Development

Abstract

Purpose of review: Human 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 findings: Human 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. Several 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.

Keywords: Cardiac tissue engineering; Cardiotoxicity; Drug screening; Pluripotent stem cells.

Fig. 1

Different engineered cardiac tissue platforms organized by relative throughput and biological relevance with a description of their advantages and limitations