Résumé :
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Much of what is known about the molecular pathways that lead to human cardiovascular disorders has come from studying animal models, particularly genetically modified mice. In some cases it is possible to translate genetic discoveries from humans to mice (e.g. non-sense mutations), but in most circumstances there are no direct correlates for human genetic variants such as single nucleotide polymorphisms (SNPs) or copy number variants. Therefore, it is imperative to replicate relevant features of human cardiovascular physiology in the context of the human genome. Recent advances in stem cell biology now raise the possibility of generating human models of cardiovascular physiology and disease.Generating patient-specific cells and tissues has recently emerged with the demonstration that exogenous expression of four proteins in human skin fibroblasts (e.g. c-MYC, KLF4, OCT4, and SOX2) is sufficient to induce pluripotency in the cells. Although so-called induced pluripotent stem cells (iPSCs) are not perfectly equivalent to human ES cells, they retain important properties of ES cells such as the capacity for long-term propagation and the ability to differentiate into all human somatic cell types. Factor-based reprogramming enables us of the long-standing ambitions of stem cell biology: the ability to generate pluripotent cells from specific patients and figuratively, move a patient's disease into the Petri dish. This will be discussed for human monogenetic cardiovascular diseases, e.g. LQT syndromes, catecholaminergic polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular dysplasia (ARVC). Recent advances describing the derivation of human iPSCs from peripheral, frozen blood brings the stem cell field an important step closer to bio-banked blood samples and eventual clinical use.Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flgel L, Dorn T, Gdel A, Hhnke C, Hofmann F, Seyfarth M, Sinnecker D, Schmig A & Laugwitz K-L (2010). Patient-specific induced pluripotent stem cell models for long-QT syndrome. N Engl J Med., Epub Jul 21.
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