Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells.
Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells.
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DOI：
10.1155/2016/1718041
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发表时间：
2016
影响因子：
4.3
通讯作者：
Lim SY
中科院分区：
文献类型：
--
作者：
Hernández D;Millard R;Sivakumaran P;Wong RC;Crombie DE;Hewitt AW;Liang H;Hung SS;Pébay A;Shepherd RK;Dusting GJ;Lim SY
背景。人类诱导多能干细胞（iPSCs）是一种有吸引力的心肌细胞来源，用于心脏修复和再生。在这项研究中，我们的目的是确定急性电刺激人类iPSCs是否可以促进其向心肌细胞分化。方法。将人iPSCs通过胚状体（EBs）培养5 d分化为心肌细胞。然后对EBs进行短暂的电刺激并镀上14天。结果。在iPS（包皮）-2细胞系中，65 mV/mm或200 mV/mm的短暂电刺激5分钟显著增加了电镀后第14天存在的跳动的EBs百分比。急性电刺激也显著增加了心脏ACTC1、TNNT2、MYH7和MYL7基因的表达。然而，电刺激的心源性效应在另一种iPS细胞系CERA007c6中不可复制。对照组和电刺激组的搏动EBs表达了各种心脏特异性转录因子和收缩肌肉标志物。跳动的EBs也显示出钙循环，并对变时剂异丙肾上腺素和氨甲酰胆碱有反应，呈浓度依赖性。结论。我们的研究结果表明，短暂的电刺激可以促进人类iPS细胞的心脏分化。短暂电刺激的致心作用取决于所使用的细胞系。
Background. Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin)-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.