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Cell Journal، جلد ۱۷، شماره Suppl ۱، صفحات ۱۲-۱۲
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عنوان انگلیسی Is-9: Induced Pluripotent Stem Cells for Disease Modeling
چکیده انگلیسی مقاله Objective: Pluripotent stem cells provide a novel tool to study cardiomyogenesis as well as mechanisms of arrhythmias under control conditions as well as in disease models. We culti-vated embryonic stem (ES) and induced pluripotent stem (iPS) cells in 3-D cell aggregates (embryoid bodies, EBs), where they differentiate into derivatives of all three germ layers. Emphasis was put on the development of human ES based screening assays to predict toxic effects and to learn about toxicological mechanisms. Materials and Methods: In order to demonstrate the suitability of pluripotent stem cells for novel disease models, reprogramming of fibroblasts from patients with LQT3, CPVT syndrome or chronic granulomatous disease (CGD) by ectopic expression of the transcription factors Oct4, Sox2, c-Myc and Klf4 resulted in generation of iPS cells for disease modelling. Results: In order to offer several cell line models of LQT3, CPVT or CGD and therefore support research on pathophysiology and new therapeutic approaches, we optimized proto-cols to differentiate induced pluripotent stem cells (iPSCs) from wild-type, X0-, AR220- and AR470-CGD patient’s fibroblasts into cardiomyocytes, neutrophils and into macrophages. Aberrant genetic clones were discarded after chromosome karyotyping and array-comparative genomic hybridization analysis. Conclusion: We describe a reproducible, simple, and efficient way to generate cardio-myocytes, neutrophils and macrophages from iPSCs and provide a new cellular model for the AR220-CGD genetic form that has not been described before. This approach may also enable patient-specific cells which are an indispensable prerequisite for a later use in clinics as well as for personalized medicine.
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نویسندگان مقاله j hescheler | j hescheler


نشانی اینترنتی http://celljournal.org/journal/article/abstract/33
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