ABSTRACT
Ischemic heart disease is one of the leading causes of fatalities globally. Ischemia-induced myocardial infarction results in cell death of cardiomyocytes, and though rapid medical intervention can reduce the risk of immediate demise, the subsequent fibrotic response that humans share with our traditional mammalian animal models (mouse, rat, rabbit, and pig) results in scar tissue formation that can ultimately lead to cardiac hypertrophy, arrhythmias, and heart failure. Unfortunately, the mammalian heart does not regenerate myocardium after injury; however, several vertebrates are capable of this feat. The processes underlying heart development are strikingly similar in all vertebrates and heart regeneration in regeneration-competent species share many similarities with developmental processes, inspiring hope that these species can ultimately teach us how to accomplish endogenous heart repair in mammals. Heart regeneration can also be approached by de novo techniques, preparing cardiac structures in vitro for later transplantation by repopulating decellularized matrix scaffolds or 3D bioprinting. However, understanding the complex architecture of the myocardium and how this interacts with cardiac function is crucial to instruct future regenerative therapies that work both on an anatomical and functional level.
