Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells.
Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells.
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DOI：
10.1371/journal.pone.0085645
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fukuda K
中科院分区：
文献类型：
--
作者：
Seki T;Yuasa S;Kusumoto D;Kunitomi A;Saito Y;Tohyama S;Yae K;Kishino Y;Okada M;Hashimoto H;Takei M;Egashira T;Kodaira M;Kuroda Y;Tanaka A;Okata S;Suzuki T;Murata M;Fujita J;Fukuda K
诱导多能干细胞（iPSC）已被提出作为遗传疾病模型和革命性临床治疗的新细胞来源。因此，人iPSC衍生的心肌细胞是心肌细胞移植治疗的潜在细胞来源。我们先前开发了一种用于人外周T细胞衍生的iPSC（TiPSC）的新生成方法，该方法使用微创方法来获得患者细胞。然而，在T细胞受体（TCR）基因中具有基因组重排的TiPSCs是否可以在体外分化为功能性心肌细胞仍然是未知的。为了解决这个问题，我们研究了形态，基因表达模式，和电生理特性的TiPSC衍生的心肌细胞分化的漂浮培养。RT-PCR和免疫组化结果显示，诱导的心肌细胞表达心肌细胞标志物和离子通道，并具有典型的心肌细胞形态。应用离子通道抑制剂的多个电极阵列也揭示了在TiPSC衍生的心肌细胞中在搏动速率和场电位波形方面的正常电生理反应。在这份报告中，我们表明，TiPSCs成功分化为心肌细胞的形态，基因表达模式，和典型的天然心肌细胞的电生理特征。因此，通过微创技术从患者获得的TiPSC衍生的心肌细胞可以成为理解心脏疾病机制的疾病模型和革命性心肌细胞疗法的细胞来源。
Induced pluripotent stem cells (iPSCs) have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs) that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR) gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies.
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影响因子：
2
作者：
Egashira, Toru;Yuasa, Shinsuke;Fukuda, Keiichi
通讯作者：
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作者：
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通讯作者：
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