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首页> 外文期刊>Nature Communications >Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues
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Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues

机译：Cardiopatch平台可实现人类多能干细胞衍生的工程心脏组织的成熟和规模化

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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 Ca2+ 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.
机译：尽管越来越多地使用人类诱导的多能干细胞来源的心肌细胞（hiPSC-CM）进行药物开发和疾病模型研究，但仍缺乏产生大型功能性心脏组织用于人类治疗的方法。在这里，我们为hiPSC-CM的3D培养和成熟提供了一个“ Cardiopatch”平台，该平台在分化5周后显示出强大的机电耦合，一致的H区，I带以及T管和M带的证据。在培养过程中，心脏补丁成熟标记和功能输出增加，接近成年心肌的值。心脏补丁可以按比例放大到临床相关尺寸，同时保留具有高传导速度和收缩应力的空间均匀特性。在裸鼠的窗室内，心肌斑块通过宿主血管进行血管化，并继续激发Ca2 +瞬变。当植入大鼠心脏时，心脏补丁会牢固植入，维持植入前的电功能，并且不会增加心律不齐的发生率。这些研究为hiPSC-CM组织在人类心脏修复中的未来使用提供了使能技术。

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