While interstitial fibrosis plays a significant role in heart failure, our understanding of disease progression in humans is limited. To address this limitation, we have engineered a cardiac-fibrosis-on-a-chip model consisting of a microfabricated device with live force measurement capabilities using co-cultured human cardiac fibroblasts and pluripotent stem cell-derived cardiomyocytes. Transforming growth factor-β was used as a trigger for fibrosis. Here, we have reproduced the classic hallmarks of fibrosis-induced heart failure including high collagen deposition, increased tissue stiffness, BNP secretion, and passive tension. Force of contraction was significantly decreased in fibrotic tissues that displayed a transcriptomic signature consistent with human cardiac fibrosis/heart failure. Treatment with an anti-fibrotic drug decreased tissue stiffness and BNP secretion, with corresponding changes in the transcriptomic signature. This model represents an accessible approach to study human heart failure in vitro, and allows for testing anti-fibrotic drugs while facilitating the real-time assessment of cardiomyocyte function.

中文翻译：

---

人心脏纤维化单芯片模型概括了疾病特征，可以用作药物测试的平台。

尽管间质纤维化在心力衰竭中起重要作用，但我们对人类疾病进展的了解仍然有限。为了解决这一局限性，我们设计了一种心脏芯片纤维化模型，该模型由具有活力测量功能的微型设备组成，该设备使用共培养的人心脏成纤维细胞和多能干细胞衍生的心肌细胞。转化生长因子-β被用作纤维化的触发剂。在这里，我们再现了由纤维化引起的心力衰竭的经典标志，包括高胶原沉积，组织硬度增加，BNP分泌和被动张力。在显示与人类心脏纤维化/心力衰竭一致的转录组特征的纤维化组织中，收缩力显着降低。用抗纤维化药物治疗可降低组织硬度和BNP分泌，并在转录组学特征上有相应的变化。该模型代表了一种可在体外研究人心力衰竭的方法，并且可以在测试抗纤维化药物的同时促进对心肌细胞功能的实时评估。