Adult cardiac cells have limited or no self-renewal capacity. Therefore, cell transplantation therapy is an attractive strategy in the treatment of heart diseases such as myocardial infarction. Given the present lack of a good cardiogenic source for transplantation among adult stem cells, lots of studies are presently focusing on methodologies to 1) efficiently generate cardiogenic cells from embryonic stem cells (hESC) and, very recently, form induced-pluripotent (iPS) stem cells, and 2) achieve a safe and efficient cell engraftment within the myocardium in animal models.

Our lab studies the mechanisms of cardiac differentiation from both murine and human ESC as this knowledge is fundamental to define secure cardiac commitment and differentiation protocols. To achieve an efficient directed differentiation of pluripotent cells, chemically-defined media are necessary that avoid the use of animal sera and components and ensure feasibility, scale-up and clinical applicability. We, among other laboratories, have ongoing projects devoted at deriving and banking new human ESC and iPS cells in chemically-defined, clinically-compliant (or GMP) conditions at the new GMP Cell Therapy Center of the Geneva University Hospitals.

In the presentation, I will discuss our recent results on the developmental maturation of human ESC-derived cardiomyocytes in culture, and their electrophysiological and pharmacological properties, in comparison to human fetal and adult cardiac cells. I will then present our recent tissue engineering strategy to regenerate the infarcted heart in a rat model of coronary occlusion. It is based on ESC seeding into fibrin-based matrices that can be functionalized with growth factors covalently bound to the fibrin network. Cardiopatches composed of cardiac-committed ESC seeded fibrin gels can be implanted in vivo. Using a rat model of myocardial infarction, we could achieve survival and extended engraftment of the infarcted area, as well as an improvement of heart function, monitored by MRI. Our encouraging results point at the feasibility and the potential benefit of cardiopatches for the therapy of myocardial infarction.