Electrical stimulation of cardiac adipose tissue-derived progenitor cells modulates cell phenotype and genetic machinery
Electrical stimulation of cardiac adipose tissue-derived progenitor cells modulates cell phenotype and genetic machinery
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DOI：
10.1002/term.1710
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发表时间：
2015-11-01
影响因子：
3.3
通讯作者：
Bayes-Genis, A.
中科院分区：
文献类型：
--
作者：
Llucia-Valldeperas, A.;Sanchez, B.;Bayes-Genis, A.
心脏组织工程的一个主要挑战是指导细胞建立被替换心肌的生理结构和功能。我们的目的是研究电刺激对心脏脂肪组织来源的祖细胞（心脏ATDPC）的心脏分化潜能的影响。测试了三种不同的电刺激方案;所选方案包括14天内以1Hz的50 mV/cm的2 ms单相方波脉冲。心脏和皮下ATDPC在生物相容性图案化表面上生长。实时荧光定量PCR和免疫细胞荧光检测心肌分化。在心脏ATDPC中，MEF 2A和加塔-4在刺激后第14天显著上调，而皮下ATDPC仅表现出Cx43表达增加。响应于电刺激，心脏ATDPC伸长，并且心脏和皮下ATDPC都按照构造的线性表面图案对齐。心脏ATDPC长度增加11.3%，而皮下ATDPC长度减少11.2%（与未刺激对照组相比，分别为p=0.013和p=0.030）。与对照组相比，当图案垂直于电场时，电刺激的细胞变得更好地与图案化表面对齐（心脏ATDPC为89.71 +/- 28.47o，皮下ATDPC为92.15 +/- 15.21o）。电刺激心脏ATDPC引起细胞表型和遗传机制的变化，使其更适合心脏再生方法。因此，在作为细胞悬浮液或在工程组织内递送之前使用电细胞训练似乎是可取的。版权所有（C）2013约翰威利父子有限公司
A major challenge of cardiac tissue engineering is directing cells to establish the physiological structure and function of the myocardium being replaced. Our aim was to examine the effect of electrical stimulation on the cardiodifferentiation potential of cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs). Three different electrical stimulation protocols were tested; the selected protocol consisted of 2ms monophasic square-wave pulses of 50mV/cm at 1Hz over 14days. Cardiac and subcutaneous ATDPCs were grown on biocompatible patterned surfaces. Cardiomyogenic differentiation was examined by real-time PCR and immunocytofluorescence. In cardiac ATDPCs, MEF2A and GATA-4 were significantly upregulated at day 14 after stimulation, while subcutaneous ATDPCs only exhibited increased Cx43 expression. In response to electrical stimulation, cardiac ATDPCs elongated, and both cardiac and subcutaneous ATDPCs became aligned following the linear surface pattern of the construct. Cardiac ATDPC length increased by 11.3%, while subcutaneous ATDPC length diminished by 11.2% (p=0.013 and p=0.030 vs unstimulated controls, respectively). Compared to controls, electrostimulated cells became aligned better to the patterned surfaces when the pattern was perpendicular to the electric field (89.71 +/- 28.47o for cardiac ATDPCs and 92.15 +/- 15.21o for subcutaneous ATDPCs). Electrical stimulation of cardiac ATDPCs caused changes in cell phenotype and genetic machinery, making them more suitable for cardiac regeneration approaches. Thus, it seems advisable to use electrical cell training before delivery as a cell suspension or within engineered tissue. Copyright (C) 2013 John Wiley & Sons, Ltd.