Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue

利用生物声学技术将人类 iPSC 衍生的心肌细胞构建成 3D 心脏组织

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作者:Vahid Serpooshan, Pu Chen, Haodi Wu, Soah Lee, Arun Sharma, Daniel A Hu, Sneha Venkatraman, Adarsh Venkataraman Ganesan, Osman Berk Usta, Martin Yarmush, Fan Yang, Joseph C Wu, Utkan Demirci, Sean M Wu

Abstract

The creation of physiologically-relevant human cardiac tissue with defined cell structure and function is essential for a wide variety of therapeutic, diagnostic, and drug screening applications. Here we report a new scalable method using Faraday waves to enable rapid aggregation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into predefined 3D constructs. At packing densities that approximate native myocardium (108-109 cells/ml), these hiPSC-CM-derived 3D tissues demonstrate significantly improved cell viability, metabolic activity, and intercellular connection when compared to constructs with random cell distribution. Moreover, the patterned hiPSC-CMs within the constructs exhibit significantly greater levels of contractile stress, beat frequency, and contraction-relaxation rates, suggesting their improved maturation. Our results demonstrate a novel application of Faraday waves to create stem cell-derived 3D cardiac tissue that resembles the cellular architecture of a native heart tissue for diverse basic research and clinical applications.

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