Endothelial cells (EC) in vivo are continuously exposed to a mechanical microenvironment from blood flow, and fluidic shear stress plays an important role in EC behavior. New approaches to generate physiologically and pathologically relevant pulsatile flows are needed to understand EC behavior under different shear stress regimes. Here, we demonstrate an adaptable pump (Adapt-Pump) platform for generating pulsatile flows from human pluripotent stem cell-derived cardiac spheroids (CS) via quantitative imaging-based signal transduction. Pulsatile flows generated from the Adapt-Pump system can recapitulate unique CS contraction characteristics, accurately model responses to clinically relevant drugs, and simulate CS contraction changes in response to fluidic mechanical stimulation. We discovered that ECs differentiated under a long QT syndrome derived pathological pulsatile flow exhibit abnormal EC monolayer organization. This Adapt-Pump platform provides a powerful tool for modeling the cardiovascular system and improving our understanding of EC behavior under different mechanical microenvironments.

中文翻译：

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使用基于定量成像的信号转导从干细胞衍生的心肌细胞产生适应性脉动流

体内内皮细胞（EC）持续暴露于血流产生的机械微环境中，流体剪切应力在 EC 行为中起着重要作用。需要新的方法来产生生理和病理相关的脉动流，以了解不同剪切应力状态下的 EC 行为。在这里，我们展示了一个适应性泵（Adapt-Pump）平台，用于通过基于定量成像的信号转导从人类多能干细胞衍生的心脏球体（CS）产生脉动流。Adapt-Pump 系统产生的脉动流可以重现独特的 CS 收缩特征，准确模拟对临床相关药物的反应，并模拟响应流体机械刺激的 CS 收缩变化。我们发现，在长 QT 综合征衍生的病理性脉动流下分化的 EC 表现出异常的 EC 单层组织。该 Adapt-Pump 平台提供了一个强大的工具，用于模拟心血管系统并提高我们对不同机械微环境下 EC 行为的理解。