Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds
Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds
复制标题
DOI：
10.1021/acsami.6b15271
复制
发表时间：
2017-03-01
影响因子：
9.5
通讯作者：
Barzin, Jalal
中科院分区：
文献类型：
--
作者：
Amirabad, Leila Mohammadi;Massumi, Mohammad;Barzin, Jalal
在胚胎心脏中，电脉冲从静脉窦以单向方式传播，似乎参与心脏发生。在这项工作中，排列和随机的聚苯胺/聚醚砜（PANI/PES）纳米纤维支架掺杂樟脑-10-磺酸（β）（CPSA）通过静电纺丝制备和用于进行电脉冲在单向和多向的方式，分别。随后设计生物反应器以将电脉冲施加到在PANI/PES支架上培养的细胞。我们从接受心胸外科手术的患者的成纤维细胞中建立了心血管疾病特异性诱导多能干细胞（CVD-iPSC）。将CVD-iPSC接种到支架上，在心肌细胞诱导因子中培养，并在生物反应器中暴露于电脉冲1小时/天，持续15天。与使用随机纤维支架的多向电刺激相比，对细胞施加单向电刺激显著增加了心肌肌钙蛋白T（cTnT+）细胞的数量。这一点通过心脏相关转录因子（NKX2.5、GATA 4和NPPA）和心脏特异性结构基因（TNNT 2）的实时聚合酶链反应得到证实。在这里，我们首次报道了以单向方式施加电脉冲，模仿心脏中电刺激的单向波，可以增加心肌细胞从CVD-iPSCs的衍生。
In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (beta) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds. We established cardiovascular disease-specific induced pluripotent stem cells (CVD-iPSCs) from the fibroblasts of patients undergoing cardiothoracic surgeries. The CVD-iPSCs were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors, and exposed to electrical impulses for 1 h/day, over a 15-day time period in the bioreactor. The application of the unidirectional electrical stimulation to the cells significantly increased the number of cardiac Troponin T (cTnT+) cells in comparison to multidirectional electrical stimulation using random fibrous scaffolds. This was confirmed by real-time polymerase chain reaction for cardiac-related transcription factors (NKX2.5, GATA4, and NPPA) and a cardiac-specific structural gene (TNNT2). Here we report for the first time that applying electrical pulses in a unidirectional manner mimicking the unidirectional wave of electrical stimulation in the heart, could increase the derivation of cardiomyocytes from CVD-iPSCs.