Fish, the better model in human heart research? Zebrafish Heart aggregates as a 3D spontaneously cardiomyogenic in vitro model system

The zebrafish (ZF) has become an essential model for biomedical, pharmacological and eco-toxicological heart research. Despite the anatomical differences between fish and human hearts, similarities in cellular structure and conservation of genes as well as pathways across vertebrates have led to an increase in the popularity of ZF as a model for human cardiac research. ZF research benefits from an entirely sequenced genome, which allows us to establish and study cardiovascular mutants to better understand cardiovascular diseases. In this review, we will discuss the importance of in vitro model systems for cardiac research and summarise results of in vitro 3D heart-like cell aggregates, consisting of myocardial tissue formed spontaneously from enzymatically digested whole embryonic ZF larvae (Zebrafish Heart Aggregate - ZFHA). We will give an overview of the similarities and differences of ZF versus human hearts and highlight why ZF complement established mammalian models (i.e. murine and large animal models) for cardiac research. At this stage, the ZFHA model system is being refined into a high-throughput (more ZFHA generated than larvae prepared) and stable in vitro test system to accomplish the same longevity of previously successful salmonid models. ZFHA have potential for the use of high-throughput-screenings of different factors like small molecules, nucleic acids, proteins and lipids which is difficult to achieve in the zebrafish in vivo screening models with lethal mutations as well as to explore ion channel disorders and to find appropriate drugs for safety screening.