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Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts.

机译:使用源自人成纤维细胞的诱导性多能干细胞生成和表征功能性心肌细胞。

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摘要

We have successfully developed both spontaneous and inductive cardiomyocyte differentiation of iPS cells reprogrammed from human foreskin fibroblasts. The reprogrammed iPS cells morphologically resemble human cardiomyocytes which can beat. RT-PCR and immunostaining show that cardiac markers are expressed that are comparable to the differentiation pattern of authentic human embryonic stem cells, indicating the existence of both immature and mature differentiated cardiomyocytes. 5-Azacytidine greatly enhanced the efficiency of cardiomyocyte differentiation, whereas dimethylsulfoxide had no effect. Low serum and bone morphogenetic protein-2 marginally improved differentiation efficiency. iPS cell-derived cardiomyocytes changed their beat frequency in response to cardiac drugs, which included ion channel blockers and alpha/beta adrenergic stimulators. Derived cardiomyocytes look promising as an in vitro system for potential drug screen and/or toxicity, making this system closer to practical use in the near future.
机译:我们已经成功地开发了从人包皮成纤维细胞重新编程的iPS细胞的自发性和诱导性心肌细胞分化。重新编程的iPS细胞在形态上类似于可以跳动的人心肌细胞。 RT-PCR和免疫染色表明,表达的心脏标志物与真实的人类胚胎干细胞的分化模式相当,这表明存在未成熟和成熟的分化心肌细胞。 5-氮杂胞苷大大提高了心肌细胞分化的效率,而二甲基亚砜则无作用。低血清和骨形态发生蛋白2略有提高分化效率。 iPS细胞衍生的心肌细胞响应心脏药物而改变了其搏动频率,心脏药物包括离子通道阻滞剂和α/β肾上腺素能刺激剂。衍生的心肌细胞有望作为一种体外系统用于潜在的药物筛选和/或毒性反应,从而使该系统在不久的将来更接近实际应用。

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