Department of Biomedical Engineering, Columbia University, 622 west 168th St., New York, NY 10032, USA.
Lab Chip. 2017 Sep 26;17(19):3264-3271. doi: 10.1039/c7lc00415j.
Current in vitro models fall short in deciphering the mechanisms of cardiac hypertrophy induced by volume overload. We developed a pneumatic microfluidic platform for high-throughput studies of cardiac hypertrophy that enables repetitive (hundreds of thousands of times) and robust (over several weeks) manipulation of cardiac μtissues. The platform is reusable for stable and reproducible mechanical stimulation of cardiac μtissues (each containing only 5000 cells). Heterotypic and homotypic μtissues produced in the device were pneumatically loaded in a range of regimes, with real-time on-chip analysis of tissue phenotypes. Concentrated loading of the three-dimensional cardiac tissue faithfully recapitulated the pathology of volume overload seen in native heart tissue. Sustained volume overload of μtissues was sufficient to induce pathological cardiac remodeling associated with upregulation of the fetal gene program, in a dose-dependent manner.
目前的体外模型在破译由容量超负荷引起的心肌肥厚的机制方面存在不足。我们开发了一种气动微流控平台，用于高通量研究心肌肥厚，该平台能够对心肌μ组织进行重复（数十万次）和稳健（数周）的操作。该平台可重复使用，可稳定且可重复地对心肌μ组织（每个组织仅包含 5000 个细胞）进行机械刺激。在该设备中产生的异质和同质μ组织在多种方案下进行气动加载，并实时进行组织表型的芯片上分析。对三维心脏组织的浓缩加载忠实地再现了在天然心脏组织中观察到的容量超负荷的病理。μ组织的持续容量超负荷足以以剂量依赖性方式诱导与胎儿基因程序上调相关的病理性心脏重构。
