Adaptable pulsatile flow generated from stem cell-derived cardiomyocytes using quantitative imaging-based signal transduction.

Adaptable pulsatile flow generated from stem cell-derived cardiomyocytes using quantitative imaging-based signal transduction.
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DOI:
10.1039/d0lc00546k
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发表时间:
2020-10-21
期刊:
影响因子:
6.1
通讯作者:
Skala MC
Skala MC
中科院分区:
工程技术1区
文献类型:
--
作者:
Qian T;Gil DA;Contreras Guzman E;Gastfriend BD;Tweed KE;Palecek SP;Skala MC

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体内内皮细胞(EC)持续暴露于血流的力学微环境中,流体切应力在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EC行为下不同的剪切应力制度。在这里,我们展示了一个自适应泵(Adapt-Pump)平台,用于通过基于定量成像的信号转导从人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CS收缩对流体机械刺激的反应变化。我们发现,在长QT综合征引起的病理性搏动流下分化的EC表现出异常的EC单层组织。这个Adapt-Pump平台为心血管系统建模提供了一个强大的工具,并提高了我们对不同机械微环境下EC行为的理解。生物驱动的脉动流是由人多能干细胞衍生的心脏细胞收缩的定量成像产生的。
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. Biologically-driven pulsatile flow is generated from quantitative imaging of contractions from human pluripotent stem cell-derived heart cells.
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