Cellular and Molecular Targets to Promote Therapeutic Cardiac Regeneration
- David SASSOON, UPMC-Sorbonne Universités , Paris (France)
- Toren FINKEL, University of Pittsburgh, Pittsburgh (USA)
- Thomas BRAUN, Max Planck Institute, Bad Nauheim (Germany)
- Richard HARVEY, Victor Chang Cardiac Research Institute, Darlinghurst (Australia)
- Jean-Sébastien HULOT, UPMC-Sorbonne Universités , Paris (France)
- Roger HAJJAR, Mount Sinai School of Medicine, New York (USA)
- Jason KOVACIC, Mount Sinai School of Medicine, New York (USA)
- Nadia ROSENTHAL, Imperial College, London (UK)
- Mark SUSSMAN, San Diego State University (USA)
The limited regenerative capacity of the mammalian heart was long thought to reflect the lack of a cellular reservoir to generate new cardiac tissue. However, numerous lines of evidence now suggest that the heart may have a significant capacity for cardiac regeneration and repair. The first major discovery was the identification of cardiac progenitor cells, which showed the ability to differentiate into the specialized cell types that make up the heart. Resident cardiac stem cells (CSCs) that persist throughout life were discovered only within the last decade and have been shown to be an important mechanism of cardiac adaptation and repair. In addition, emerging data now suggest that cardiomyocyte de-differentiation and proliferation may be another major component of the cardiac adaptation/repair program. Cardiomyocyte de-differentiation may either lead directly to new cardiac muscle formation or proceed through a transient CSC state. Furthermore, a resident population of adult mesenchymal stem cells that originate in the epicardium has emerged as a major potential contributor to cardiac repair. Collectively, these data suggest that the adult heart is likely to have significant intrinsic regenerative capacity, but the regulatory mechanisms that direct and limit this process remain to be delineated.
At present, no scientific consensus has emerged regarding the processes regulating cardiac regeneration. The rationale for this network lies in the need for defining the mechanisms regulating and ultimately limiting regenerative responses of the adult heart. A shared, robust platform of in vitro and in vivo models will facilitate characterization of resident cardiac stem and progenitor cells, and a thorough dissection of the process of direct cardiac de-differentiation. Unraveling the complex and poorly understood processes mediating the age-dependent decline in cardiovascular stem cell efficacy and regenerative capacity is a core objective of this network. These mechanistic studies will lead to the identification of targets that can be modulated to boost the endogenous regenerative potential of the adult mammalian heart, including the use of small molecules that stimulate the mobilization of endogenous CSCs or transiently activate de-differentiation. With a little help the heart may just be capable of repairing itself in the setting of injury or disease.
More information on http://www.cardiostemnet.com