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Human derived cardiomyocytes: A decade of knowledge after the discovery of induced pluripotent stem cells

机译:人源性心肌细胞:发现诱导性多能干细胞后的十年知识

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摘要

Ten years ago Yamanaka's lab identified a way to reprogram terminally differentiated cells to a pluripotent state, similar to that of embryonic stem cell. This procedure opened the road for the generation of postmitotic human cells, that have completely lost the replication potential. The initial excitement waned when it was observed that the cells produced by this method are somehow immature and do not resemble the adult phenotype. In the absence of cellular markers that recognize the various maturation steps of induced pluripotent stem cell-derived human cardiomyocytes, we propose to follow their maturation looking at their electrophysiological profile. For this reason, we are first reviewing the most common methods of differentiation, from the preliminary complex procedures to the newly-identified two-step protocols and, second, we report the electrical characteristics of the cells, through electrophysiological analysis of ionic currents that give rise to the action potential. We are aware that each protocol leads to the generation of different cardiomyocyte precursors, thus suggesting the need for a wider standardization. The identification of the electrophysiological characteristics of the cells could help in identifying the type and the maturation stage of the obtained cardiomyocyte, thus compensating for the lack of specific markers.
机译:十年前,Yamanaka的实验室确定了一种将最终分化的细胞重编程为多能态的方法,类似于胚胎干细胞。该程序为完全丧失复制潜力的有丝分裂后人类细胞的产生开辟了道路。当观察到通过这种方法产生的细胞某种程度上不成熟并且不类似于成年表型时,最初的兴奋感减弱了。在缺乏识别诱导的多能干细胞衍生的人心肌细胞的各种成熟步骤的细胞标记物的情况下,我们建议遵循其成熟度,以观察其电生理特征。因此,我们首先审查最常见的分化方法,从初步的复杂程序到新近确定的两步方案,其次,我们通过对离子电流进行电生理分析来报告细胞的电特性。发挥动作潜力。我们知道,每种方案都会导致产生不同的心肌前体细胞,因此表明需要更广泛的标准化。鉴定细胞的电生理特性可以帮助鉴定获得的心肌细胞的类型和成熟阶段,从而弥补缺乏特异性标记物的不足。

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