Programming the Failing Heart to a Regenerative State

• Mauro GIACCA, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

• Richard LEE, Brigham and Women's Hospital, Boston, Massachusetts, USA

Given the global burden of heart disease and its increasing prevalence in aging populations, one of the most important challenges of modern medecine is the development of strategies to regenerate the human heart.

 This network is focused on manipulating the regenerative potential of endogenous cells of the heart instead of adding exogenous cells. As mouse fibroblasts can be reprogrammed toward a cardiac cell fate in vitro and in vivo, improving cardiac function and reducing adverse ventricular remodeling in mice, the network will use a combination of factors, similar to but distinct from the mouse factors, together with a microRNA, to reprogram adult human fibroblasts into cardiomyocyte-like cells.

The members of this network will collaboratively develop a series of interrelated strategies to enhance cardiac regeneration and repair by the reprogramming of non-cardiac cells, like macrophages, into cardiomyocytes and by the homing of cardiac regenerating cells.  Through activation and stimulation of repair mechanisms, they will define and optimize methods for enhancing function of injured mammalian hearts, and will extend these studies to a large animal model to bring this knowledge toward translation, in either mini-pigs or non-human primates and into human engineered myocardium.

This will provide new therapeutic approaches to enhance the limited capacity of the heart to regenerate with applications in diverse cardiac disorders, including both genetic and acquired forms of heart disease.