An iPS-derived in vitro model of human atrial conduction.
An iPS-derived in vitro model of human atrial conduction.
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DOI：
10.14814/phy2.15407
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发表时间：
2022-09
影响因子：
2.5
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中科院分区：
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房颤（AF）是美国最常见的心律失常，影响大约十分之一的成年人，其患病率预计将随着人口老龄化而上升。房颤的治疗选择是有限的；此外，新疗法的发展受到以下因素的限制：(1)关于人类心房电生理终点（例如传导速度[CV]）的知识有限；(2)准确的实验模型。在这里，我们测量了CV和不应期，随后计算了体内（4名房颤患者和4名对照组）和离体（人类心脏心房切片）的传导波长。然后，我们利用诱导多能干细胞（iPS）建立了体外人心房传导模型。该模型由iPS衍生的人心房心肌细胞镀在微图案线性1D螺旋设计的Matrigel上组成。体外模型的CV （34-41 cm/s）比2D对照（7-9 cm/s）快近5倍，与体内（40-64 cm/s）和离体（28-51 cm/s）测量结果相似。我们的iPS衍生的体外模型概括了体内心房传导的关键特征，可能是一种有用的方法，可以增强我们对房颤的理解和模型患者特异性疾病。我们提出了一个诱导多能干细胞衍生的体外人心房传导模型。该设计包括一个线性1D螺旋设计，显着增加传导速度，从而概括了体内心房传导的关键特征。该模型可能是一种有用的方法，以加强我们对房颤和模型患者特异性疾病的理解。
Atrial fibrillation (AF) is the most common arrhythmia in the United States, affecting approximately 1 in 10 adults, and its prevalence is expected to rise as the population ages. Treatment options for AF are limited; moreover, the development of new treatments is hindered by limited (1) knowledge regarding human atrial electrophysiological endpoints (e.g., conduction velocity [CV]) and (2) accurate experimental models. Here, we measured the CV and refractory period, and subsequently calculated the conduction wavelength, in vivo (four subjects with AF and four controls), and ex vivo (atrial slices from human hearts). Then, we created an in vitro model of human atrial conduction using induced pluripotent stem (iPS) cells. This model consisted of iPS‐derived human atrial cardiomyocytes plated onto a micropatterned linear 1D spiral design of Matrigel. The CV (34–41 cm/s) of the in vitro model was nearly five times faster than 2D controls (7–9 cm/s) and similar to in vivo (40–64 cm/s) and ex vivo (28–51 cm/s) measurements. Our iPS‐derived in vitro model recapitulates key features of in vivo atrial conduction and may be a useful methodology to enhance our understanding of AF and model patient‐specific disease. We present an induced pluripotent stem‐derived in vitro model of human atrial conduction. The design includes a linear 1D spiral design that significantly increases conduction velocity and thus recapitulates key features of in vivo atrial conduction. The model may be a useful methodology to enhance our understanding of atrial fibrillation and model patient‐specific disease.