Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.
Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.
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DOI：
10.1021/acs.nanolett.6b02093
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发表时间：
2016-07-13
期刊：
影响因子：
10.8
通讯作者：
Mei Y
中科院分区：
文献类型：
--
作者：
Richards DJ;Tan Y;Coyle R;Li Y;Xu R;Yeung N;Parker A;Menick DR;Tian B;Mei Y
人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）技术的进步已经显示出提供治疗心血管疾病的患者特异性再生细胞治疗策略的有希望的潜力。尽管取得了进展，但hiPSC-CM的非特异性、不发达表型已显示出移植后的致瘤风险和有限的功能改善。为了解决这个问题，组织工程策略已经利用外源性和内源性刺激来加速hiPSC-CM的发育。外源性电刺激提供了一种仿生起搏器样刺激，已被证明可以提高组织工程心脏结构的电性能。最近，我们证明了将导电硅纳米线掺入hiPSC心脏球体通过改善内源性电微环境导致hiPSC-CM的高级结构和功能发育。在此，我们推断，毛化hiPSC心脏球体的增强的内源性电微环境将与外源性电刺激协同作用，以进一步促进毛化hiPSC心脏球体的功能发育。我们首次报道了纳米线和电刺激的组合增强了细胞-细胞连接的形成，改善了收缩机制的发展，并导致hiPSC心脏球体的自发搏动率显著降低。这些进展解决了在心脏发育和转化研究中使用hiPSC-CM的关键挑战，并为下一代心脏修复提供了先进的细胞递送载体。
The advancement of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs. Exogenous electrical stimulation provides a biomimetic pacemaker-like stimuli that has been shown to advance the electrical properties of tissue engineered cardiac constructs. Recently, we demonstrated that the incorporation of electrically conductive silicon nanowires to hiPSC cardiac spheroids led to advanced structural and functional development of hiPSC-CMs by improving the endogenous electrical microenvironment. Here, we reasoned that the enhanced endogenous electrical microenvironment of nanowired hiPSC cardiac spheroids would synergize with exogenous electrical stimulation to further advance the functional development of nanowired hiPSC cardiac spheroids. For the first time, we report that the combination of nanowires and electrical stimulation enhanced cell-cell junction formation, improved development of contractile machinery, and led to a significant decrease in the spontaneous beat rate of hiPSC cardiac spheroids. The advancements made here address critical challenges for the use of hiPSC-CMs in cardiac developmental and translational research and provide an advanced cell delivery vehicle for the next generation of cardiac repair.