Résumé :
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Methods have been developed for efficient and reproducible differentiation of human embryonic stem cells to cardiomyocytes. This has facilitated microarray analysis of gene expression patterns during human cardiomyocyte differentiation. Stages of nascent mesoderm and transition to cardiac progenitor cells are clearly identifiable, temporally distinct and can be controlled by exogenous growth factors. Apart from genes that would have been expected on the basis of studies of heart development in multiple species, 15 novel or unique genes were identified. Functional analysis of these in zebrafish and mice has indicated several that might be associated with congenital heart defects in humans. This is currently being investigated in DNA databases of patients with heart defects with view to developing new paradigms for prenatal genetic diagnosis. More challenging has been sustained improvement in cardiac function in mice after myocardial infarction. Despite good graft survival for up to 9 months, the presence of stem cell derived cardiomyocytes and organized in vessels that connect with the mouse vasculature, functional improvement are only detectable up to 4 weeks post transplantation; thereafter, controls recover to the same extent as mice receiving stem cell derived cardiomyocytes.
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