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.

中文翻译：

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用于病理性心脏肥大的高通量研究的微流控平台

目前体外这些模型在破译由容量超负荷引起的心脏肥大的机制方面是不足的。我们开发了一种用于心脏肥大的高通量研究的气动微流控平台，该平台能够重复（数十万次）和强大（数周以上）处理心脏组织。该平台可重复使用，以稳定，可重复地对心脏组织进行机械刺激（每个组织仅包含5000个细胞）。装置中产生的异型和同型μ组织在一定范围内被气动加载，并对组织表型进行实时的芯片分析。三维心脏组织的集中负荷忠实地概括了天然心脏组织中见到的容量超负荷的病理。