Résumé :
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Multiple in vitro model systems are currently available to evaluate structure/function relationships in the cardiovascular system. However, within the framework of studies aiming at regenerative medicine in cardiology using embryonic stem cells, it occurred to us that an in vitro model that would allow analysing the anatomical and functional integration of cells into the myocardium was missing. We, therefore, designed such a model by making use of the fact that, in contrast to isolated cells, the anatomic and functional integrity of organotypic tissue slices may remain preserved over very long periods of time. Ventricular slices (1mm-thickness) were cut from 3 day-old rat hearts and placed on millicell membranes. Ventricular tissue slices exhibited normal histology for months. In parallel, starting a few days after plating and continuing up to the end of the longest experiments (3 months), ventricular slices exhibited regular beating, with calcium transients that could be modulated by epinephrine. Similar results were obtained using human heart slices from an 8 week-old donor embryo. Following implantation into rat ventricular slices, human embryonic stem cells survived and differentiated into cardiomyocytes over months. Integration of these human cardiomyocytes into the rat slices did not alter the rythmicity the rate of beating, in contrast to the deleterious effect recorded when control HEK cells were implanted. Altogether, our results point to heart organotypic slice cultures not only as a substrate for cell growth and differentiation but also as a functional in vitro model for experimental therapeutic analyses.
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