Translating human pluripotent stem cells from heart disease models to cardiac repair

European Coordinator:

Michel PUCEAT, Université d'Aix-Marseille (France)

North American Coordinator:

Andre TERZIC, Mayo Clinic, Rochester (USA)

Members:

Lucienne CHATENOUD, Université Paris Descartes, INSERM U1013, Paris (France)
Jacques DE BAKKER, Academic Medical Center, ICIN, Amsterdam (The Netherlands)
Sian HARDING, Imperial College, London (UK)
Philippe MENASCHE, Université Paris Descartes, INSERM U633, Paris (France)
Mark MERCOLA, Stanford University, Palo Alto (USA)
Shoukhrat MITALIPOV, Oregon Health and Science University, Beaverton (USA)
Joseph WU, Stanford University (USA)

Despite advances in treatment, heart failure remains a leading cause of hospitalization and death worldwide. There are numerous conditions that can lead to heart failure, but the fundamental common problem is a loss of healthy, functioning cardiac muscle cells, which the heart is unable to replace due to its limited regenerative capacity. Providing new healthy cells is therefore a therapeutic possibility, now being actively pursued around the world.

There are three broad categories of cells that may regenerate heart muscle cells: embryonic stem cells, induced pluripotent stem cells, and reprogrammed adult cardiac cells. These categories of cells vary in their degree of pluripotency, or their capacity to differentiate into various cell types. At one end of the spectrum, embryonic stem cells have essentially limitless potential to become any kind of cell in the body. Induced pluripotent stem cells are adult cells, such as skin cells, that have been manipulated to force the expression of genes necessary for stem cell properties. The strategy of reprogramming adult cardiac cells seeks augment the regenerative capacity of cells that already have properties of cardiac muscle.

This network will determine the effectiveness of these different cell populations as treatments for heart failure. The investigators will delineate the genetic, epigenetic, metabolic, and physiologic properties of the different cell types, and determine the molecular signals that push them towards becoming cardiac muscle cells. The network will make use of special expertise in cell-delivery approaches to maximize cell survival and integration into the heart; in strategies to protect the cells from harmful immunologic responses; and in minimally invasive techniques to track the fate of the cells in living animals. Finally, the network will create induced pluripotent stem cells from patients with heart failure to better comprehend the obstacles to their therapeutic capacity, such as the effect of aged mitochondria (cellular compartments that produce the energy supply for the cell).