An in vitro beating heart model for long-term assessment of experimental therapeutics.

Within the framework of studies aiming at regenerative medicine for cardiovascular disease, we have developed an in vitro model to analyse human embryonic stem (ES) cell engraftment into the myocardium. This model is based on organotypic rat ventricular slices maintained in culture at the air-medium interface on semi-porous membranes. Survival and differentiation of human cardiomyocytes derived from ES cells were then assessed for several months. In addition, we observed that ventricular tissue slices not only exhibited normal histology, but also rhythmic contractions till the end of the experiments (up to 3 months). Similar results were obtained using ventricular slices obtained from two human foetuses at 8 and 9.5 weeks of age. Calcium transients were associated with the beating frequency, and the pattern was modulated in a dose-dependent manner by epinephrine. Our data suggest that the organotypic heart slice culture on semi-porous membranes is a relevant in vitro heart model for long-term histological and physiological studies.