Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Nat Commun. 2017 Nov 28;8(1):1825. doi: 10.1038/s41467-017-01946-x.
Despite increased use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for drug development and disease modeling studies, methods to generate large, functional heart tissues for human therapy are lacking. Here we present a "Cardiopatch" platform for 3D culture and maturation of hiPSC-CMs that after 5 weeks of differentiation show robust electromechanical coupling, consistent H-zones, I-bands, and evidence for T-tubules and M-bands. Cardiopatch maturation markers and functional output increase during culture, approaching values of adult myocardium. Cardiopatches can be scaled up to clinically relevant dimensions, while preserving spatially uniform properties with high conduction velocities and contractile stresses. Within window chambers in nude mice, cardiopatches undergo vascularization by host vessels and continue to fire Ca transients. When implanted onto rat hearts, cardiopatches robustly engraft, maintain pre-implantation electrical function, and do not increase the incidence of arrhythmias. These studies provide enabling technology for future use of hiPSC-CM tissues in human heart repair.
尽管人类诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）在药物开发和疾病建模研究中的应用越来越多，但缺乏生成用于人类治疗的大型功能性心脏组织的方法。在这里，我们提出了一种“Cardiopatch”平台，用于 hiPSC-CMs 的 3D 培养和成熟，经过 5 周的分化后，显示出强大的机电耦合、一致的 H 区、I 带，以及 T 小管和 M 带的证据。Cardiopatch 的成熟标志物和功能输出在培养过程中增加，接近成年心肌的水平。Cardiopatch 可以扩大到临床相关的尺寸，同时保持空间均匀的特性，具有较高的传导速度和收缩应力。在裸鼠的窗室中，Cardiopatch 会被宿主血管进行血管化，并继续产生 Ca 瞬变。当植入大鼠心脏时，Cardiopatch 能够有效地移植，保持植入前的电功能，并且不会增加心律失常的发生率。这些研究为未来在人类心脏修复中使用 hiPSC-CM 组织提供了可行的技术。
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