Reprogrammed Cardiac Fibroblasts to the Rescue of Heart Failure

In Vivo Reprogramming of Murine Cardiac Fibroblasts Into Induced Cardiomyocytes Qian et al Nature . 2012;485:593–598. Heart Repair by Reprogramming Nonmyocytes With Cardiac Transcription Factors Song et al Nature . 2012;485:599–604.Heart failure is a growing problem, but 2 recent reports in Nature provide new insights into the role of reprogramming cardiac fibroblasts in damaged mouse hearts into cardiac myocytes. The enhanced benefits of cardiac fibroblast conversion into cardiomyocytes may provide new therapeutic venues for the treatment of heart failure. Heart failure is a leading cause of death worldwide. It is often the result of acute or chronic ischemic heart injury. Because the adult heart does not have the capacity to replace the injured cardiomyocytes, this inevitably leads to loss of cardiomyocytes, fibrosis, and loss of pump function. Many efforts have been put into cell-based therapy, in hope that exogenously delivered cells could replace injured cardiomyocytes and restore pump function. However, efforts up to date only led to a limited degree of success. In a recent issue of Nature, Qian et al from the Srivastava laboratory and Song et al from the Olson laboratory have made a major breakthrough in the research for the treatment of heart failure.1,2 The two groups have independently shown that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in vivo, accompanied by pronounced improvement of cardiac contractile function after myocardial infarction.In 1987, Davis et al3 first demonstrated that a single transcription factor, MyoD1, can convert fibroblasts into myoblasts. The search for a “CardioD” has been underway for many years, but only Mesp1 has recently been reported as the likely candidate.4,5 Shinya Yamanaka's discovery of induced pluripotent stem cells (iPSCs) has injected new hope to this line of research: patients' own cells can be reprogrammed into a stem cell fate and then directed to the desired cell type for therapy.6 Inspired by Yamanaka's work, others have proven that …