Mechanisms Underlying Cardiomyocyte Development: Can We Exploit Them to Regenerate the Heart?

It is well established that the adult mammalian cardiomyocytes retain a low capacity for cell cycle activity; however, it is insufficient to effectively respond to myocardial injury and facilitate cardiac regenerative repair. Lessons learned from species in which cardiomyocytes do allow for proliferative regeneration/repair have shed light into the mechanisms underlying cardiac regeneration post-injury. Importantly, many of these mechanisms are conserved across species, including mammals, and efforts to tap into these mechanisms effectively within the adult heart are currently of great interest.

Targeting the endogenous gene regulatory networks (GRNs) shown to play roles in the cardiac regeneration of conducive species is seen as a strong approach, as delivery of a single or combination of genes has promise to effectively enhance cell cycle activity and CM proliferation in adult hearts post-myocardial infarction (MI). In situ re-induction of proliferative gene regulatory programs within existing, local, non-damaged cardiomyocytes helps overcome significant technical hurdles, such as successful engraftment of implanted cells or achieving complete cardiomyocyte differentiation from cell-based approaches. Although many obstacles currently exist and need to be overcome to successfully translate these approaches to clinical settings, the current efforts presented here show great promise.