用于高通量药物测试的人类ipsc来源的心脏微组织的快速3D生物打印

Kathleen L. Miller , Yi Xiang , Claire Yu , Jacob Pustelnik , Jerry Wu , Xinyue Ma , Toshikatsu Matsui , Kenichi Imahashi , Shaochen Chen
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引用次数: 16

摘要

由于心脏病是世界上一个普遍的问题,对准确和高通量药物检测的需求是至关重要的。3D心脏组织是很有前途的模型,因为它们可以概括影响药物反应的细胞-细胞、细胞-基质和细胞-组织相互作用。使用内部开发的微连续光学打印系统,我们在短短几秒钟内创建了一个心脏微组织,并在一个足够小的水凝胶支架上进行微尺度对齐,该支架可以安装在96孔板上。这种3D打印的、不对称的、基于悬臂的组织支架允许人们直接测量由跳动的微组织产生的变形。7天后,微组织表现出高水平的肌瘤组织和成熟标志物表达的显著增加。不同剂量的异丙肾上腺素和维拉帕米两种代表性药物对心脏微组织进行了验证,显示出相应的可测量的跳动频率和位移变化。这种在多孔板上快速生物打印心脏微组织的方法为药物发现的高通量筛选提供了一种很有前途的解决方案。
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Rapid 3D BioPrinting of a human iPSC-derived cardiac micro-tissue for high-throughput drug testing

With cardiac disease a reigning problem in the world, the need for accurate and high-throughput drug testing is paramount. 3D cardiac tissues are promising models, as they can recapitulate the cell-cell, cell-matrix, and cell-tissue interactions that impact response to a drug. Using an in-house developed micro-continuous optical printing system, we created a cardiac micro-tissue in mere seconds with microscale alignment cues in a hydrogel scaffold that is small enough to fit in a 96-well plate. The 3D printed, asymmetric, cantilever-based tissue scaffold allows one to directly measure the deformation produced by the beating micro-tissue. After 7 days, the micro-tissue exhibited a high level of sarcomere organization and a significant increase in maturity marker expression. The cardiac micro-tissues were validated against two representative drugs, isoproterenol and verapamil at various doses, showing corresponding and measurable changes in beating frequency and displacement. Such rapidly bioprinted cardiac micro-tissues in a multi-well plate offer a promising solution for high-throughput screening in drug discovery.

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来源期刊
Organs-on-a-chip
Organs-on-a-chip Analytical Chemistry, Biochemistry, Genetics and Molecular Biology (General), Cell Biology, Pharmacology, Toxicology and Pharmaceutics (General)
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审稿时长
125 days
期刊最新文献
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