Engineered electrical conduction tract restores conduction in complete heart block: from in vitro to in vivo proof of concept.
Engineered electrical conduction tract restores conduction in complete heart block: from in vitro to in vivo proof of concept.
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DOI：
10.1016/j.jacc.2014.09.056
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发表时间：
2014-12-23
影响因子：
24
通讯作者：
Marbán E
中科院分区：
文献类型：
--
作者：
Cingolani E;Ionta V;Cheng K;Giacomello A;Cho HC;Marbán E
心脏电传导延迟和阻断会导致心律紊乱，如完全性心脏传导阻滞，这可能是致命的。标准护理依赖于电子设备来人工恢复同步。我们试图通过设计用于传播电脉冲的传导束来创造一种治疗这种疾病的新方法。我们试图创造一种使用工程导电束(EECT)治疗心脏传导障碍的新方法。将顺磁珠与心肌细胞表面抗原γ-肌聚糖抗体偶联，与新鲜分离的新生大鼠心室肌细胞(NRVM)混合。利用磁场对线性EECT进行了构图。在体外传导阻断模型中，EECT被设计成连接两个独立跳动的NRVM单分子层，实现了协调的电活动，动作电位通过EECT从一个区域传播到另一个区域。用心脏来源的基质细胞刺激EECT可以产生稳定的结构和高度可重复性的传导速度。EECT体内移植可恢复完全性心脏传导阻滞大鼠的房室传导。组织工程化的导电管可以在心脏内重建电传导。原则上，这种新的方法不仅可以用于治疗心律失常，还可以用于修复其他器官。
Cardiac electrical conduction delays and blocks cause rhythm disturbances such as complete heart block, which can be fatal. Standard of care relies on electronic devices to restore synchrony artificially. We sought to create a new modality to treat such disorders by engineering electrical conduction tracts designed to propagate electrical impulses. We sought to create a new approach to treat cardiac conduction disorders using engineered electrical conduction tracts (EECT). Paramagnetic beads were conjugated with an antibody to γ-sarcoglycan, a cardiomyocyte cell-surface antigen, and mixed with freshly-isolated neonatal rat ventricular cardiomyocytes (NRVMs). A magnetic field was used to pattern a linear EECT. In an in vitro model of conduction block, EECT, patterned so as to connect 2 independently beating NRVM monolayers, achieved coordinated electrical activity, with action potentials propagating from 1 region to the other via EECT. Spiking EECT with heart-derived stromal cells yielded stable structures with highly reproducible conduction velocities. Transplantation of EECT in vivo restored atrio-ventricular conduction in a rat model of complete heart block. A tissue-engineered electrical conduction tract can re-establish electrical conduction in the heart. This novel approach could, in principle, be used, not only to treat cardiac arrhythmias, but also to repair other organs.