Heart Regeneration

Abstract

Is reprogramming a physiological repair mechanism occurring during cardiac regeneration? Heart failure is one of the main health problems worldwide, and the urgent medical needs relating to it have positioned cardiovascular research as one of the most actively evolving fields in regenerative medicine. Many different strategies aiming to revert, palliate, or ameliorate the deleterious effects of heart failure have been intensively pursued, and excellent reviews on the topic exist.1–3 Briefly, approaches used to tackle cardiac repair have been focused mainly on the use of stem cells to replenish lost muscle mass (cell transplantation or mobilization of resident cardiac stem cells), reduction of cardiomyocyte hypertrophy or prevention of fibrosis, promotion of angiogenesis, and, most recently, in vivo reprogramming strategies.4–6 Although these significant advances are contributing to the development of more efficient therapies, successful and efficient heart repair strategies are by and large still lacking. Are there alternative approaches beside those mentioned above? A possible line of attack is to look at how nature deals with this issue. Regenerative animal models are able to regenerate the heart completely.7 They do so by preventing scar formation, replenishing lost muscle tissue, and eliciting a controlled proangiogenic response. All these processes lead to a complete repair of the injured heart. Whereas it is well known that these processes occur naturally only in lower vertebrates, it has been a long established dogma that the mammalian heart is not able to regenerate. However, although the adult mammalian heart is not able to regenerate after massive myocardial damage, it can activate a healing process resembling that of regenerative organisms.8 Although the numbers of newly generated cardiomyocytes are insufficient for healing of the heart, it is clear that endogenous repair mechanisms are present in the mammalian heart, thus providing a potential …