一种用于建立和分析稳定人体器官模型的支柱和灌注板平台。
A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis.
发表日期:2023 Aug 24
作者:
Soo-Yeon Kang, Masaki Kimura, Sunil Shrestha, Phillip Lewis, Sangjoon Lee, Yuqi Cai, Pranav Joshi, Prabha Acharya, Jiafeng Liu, Yong Yang, J Guillermo Sanchez, Sriramya Ayyagari, Eben Alsberg, James M Wells, Takanori Takebe, Moo-Yeal Lee
来源:
Cellular & Molecular Immunology
摘要:
人类器官样品具有潜力通过提供与体内相似的多细胞结构和功能来彻底改变体外疾病模型。然而,这种创新且不断发展的技术仍然存在易于使用流体系统与相对较大的器官样品兼容的难题,由于器官样品分化过程的繁琐和规模化以及质量控制的困难,因此对化合物进行高通量筛选(HTS)的测定效能和重复性有限。本研究通过应用"微阵列三维(3D)生物打印"技术和相关的支柱和灌注板,克服了这些挑战,用于人类器官样品的培养和分析。在支柱板上展示了高精度、高通量的干细胞打印和封装技术,该技术与补充的深孔板和灌注孔板相结合,用于静态和动态器官样品培养。在水凝胶中生物打印的细胞和小球体被分化为肝脏和肠道器官样品以进行原位功能测定。支柱/灌注板与标准384孔板和HTS设备兼容,因此可以轻松地应用于当前的药物发现工作中。本文受版权保护。保留所有权利。这篇文章受版权保护。保留所有权利。
Human organoids have potential to revolutionize in vitro disease modeling by providing multicellular architecture and function that are similar to those in vivo. This innovative and evolving technology, however, still suffers from assay throughput and reproducibility to enable high-throughput screening (HTS) of compounds due to cumbersome organoid differentiation processes and difficulty in scale-up and quality control. Using organoids for HTS is further challenged by lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Here, we overcome these challenges by engineering "microarray three-dimensional (3D) bioprinting" technology and associated pillar and perfusion plates for human organoid culture and analysis. High-precision, high-throughput stem cell printing and encapsulation techniques were demonstrated on a pillar plate, which was coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels were differentiated into liver and intestine organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384-well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.