Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue.
Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue.
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DOI：
10.1016/j.biomaterials.2017.03.037
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发表时间：
2017-07
期刊：
影响因子：
14
通讯作者：
Wu SM
中科院分区：
文献类型：
--
作者：
Serpooshan V;Chen P;Wu H;Lee S;Sharma A;Hu DA;Venkatraman S;Ganesan AV;Usta OB;Yarmush M;Yang F;Wu JC;Demirci U;Wu SM
具有确定的细胞结构和功能的生理相关的人类心脏组织的创建对于各种各样的治疗、诊断和药物筛选应用是必不可少的。在这里，我们报告了一种新的可扩展的方法，使用法拉第波，使人类诱导多能干细胞衍生的心肌细胞（hiPSC-CM）快速聚集成预定义的3D结构。在接近天然心肌（108-109个细胞/ml）的填充密度下，与具有随机细胞分布的构建体相比，这些hiPSC-CM衍生的3D组织显示出显著改善的细胞活力、代谢活性和细胞间连接。此外，构建体内的图案化hiPSC-CM表现出显著更高水平的收缩应力、搏动频率和收缩-松弛速率，表明它们的成熟改善。我们的研究结果证明了一种新的应用法拉第波创建干细胞衍生的三维心脏组织，类似于天然心脏组织的细胞结构，用于各种基础研究和临床应用。创建3D心脏组织类似物的生物工程方法的示意图总结。A：人诱导多能干细胞（hiPSC）的培养和心肌细胞（CM）分化。B：hiPSC-CM在纤维蛋白预聚物中的法拉第波图案化，产生高度堆积的3D细胞构建体。丙：细胞包封在3D纤维蛋白水凝胶中并在体外培养，导致形成表现出生理相关CM密度和收缩功能的相互连接的细胞带。
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. Schematic summary of the bioengineering approach to create 3D cardiac tissue analogues. A: Culture and cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs). B: Faraday wave patterning of hiPSC-CMs in fibrin prepolymer, generating highly-packed 3D cell construct. C: Cell encapsulation in 3D fibrin hydrogel and culture in vitro, leading to the formation of inter-connected cell bands that exhibit physiologically-relevant CM density and contractile function.