Manipulating myocyte cell cycle control for cardiac repair

A fundamental tenet in cardiac biology, namely that the heart is a postmitotic organ incapable of regeneration, has recently been challenged. According to the traditional belief, the number of cardiac myocytes we are born with is all we will have for the rest of our lives. If myocytes die (e.g. as the result of infarction), they cannot be renewed. This is why myocardial infarction (MI) and its consequences, such as congestive heart failure, continue to be a major cause of death worldwide despite the considerable therapeutic advances that have been made over the past decades.In one attempt to evade this dilemma, cell replacement strategies are currently being investigated for their therapeutic potential to restore cardiac function. Indeed, a growing body of evidence from both basic animal studies and clinical trials indicates that cell-based strategies using different stem cell populations such as embryonic stem cells, skeletal myoblasts, haematopoietic stem cells, endothelial progenitor cells, and mesenchymal stem cells might be promising.1,2 According to these studies, improvements in clinical symptoms, left-ventricular function, and myocardial perfusion are feasible with cell therapy. However, there is an ongoing controversy about the underlying mechanisms and, particularly, the capability of the different implanted progenitor cells to transdifferentiate and what the essential prerequisites for this transdifferentiation might be. Only on understanding these mechanisms and, likely, through the appropriate priming and engineering of the cells to be implanted regeneration by this approach might be achieved.Another approach to induce cardiac regeneration for repair after injury would be to reverse the terminal differentiation, as many mammalian tissues respond to injury by activating … *Corresponding author. Tel: +49 341 972 5810; fax: +49 341 972 5809. E-mail address: alexander.deten{at}izi.fraunhofer.de