Résumé :
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Duchenne muscular dystrophy (DMD) is a genetic disease with an X-linked recessive pattern of inheritance. It affects one in 3,500 boys at birth. Muscular dystrophies are caused by mutation of the same gene encoding for the dystrophin. This protein is expressed in the skeletal muscle, the heart and the digestive system and is essential to the maintenance of cellular architecture. Thus, a defect of the dystrophin involves the rupture of this bond and causes a weakness of the muscle cell membrane. In the late-stage disease, the majority of DMD patients develop a dilated cardiomyopathy. For the moment, there is no curative treatment available. Embryonic stem (ES) cells, which can divide indefinitely and give rise to many cellular types including cardiomyocytes, represent a very promising tool for a cell therapy approach of the cardiac pathology in this disease. However, defining the appropriate cell population to transplant is still in question. The aim of this project is to obtain an homogeneous and self-renewable population of cardiac precursors from embryonic stem cells, based on two types of approaches: (i) co-cultures with visceral endoderm-like (END-2) cells or new-born rat heart fibroblasts which are potentially able to induce cardiac differentiation and (ii) using growth factors that promote cardiac differentiation (BMP2, Wnt3a). The preliminary results showed that addition of Wnt3a during the first three days of differentiation of mESc increase the proportion of contracting myocytes. Moreover, we have established co-culture of hESc with new-born rat heart fibroblasts and results are encouraging to follow through these studies.
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