Abstract
In this short review, we draw parallels and stress differences between heart regeneration in mice and human, from a bioengineering perspective. As the prevailing dogma that the adult heart is completely post-mitotic is starting to change, there are multiple opportunities for augmenting the limited but definitive turnover of cardiomyocytes, to the extent necessary developing clinically relevant modalities for enhancing heart repair. We discuss some of the most promising among these new directions: mobilization of paracrine signaling by therapeutic cells, cell-free therapy of the heart using extracellular vesicles, and direct reprograming of endogenous cells. These new directions share the cell-free, mechanistic approach to heart repair that could be translated into the clinic faster and safer than the traditional cell therapies.