Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2020,（8）
• 所属期刊栏目: Articles
• 页码范围: 630-643
• 页数: 14页
• 语种: 英文
• DOI: 10.1093/jmcb/mjaa036

摘要

The recent advent of robust methods to grow human tissues as 3D organoids allows us to recapitulate the 3D architecture of tumors in an in vitro setting and offers a new orthogonal approach for drug discovery. However, organoid culturing with extracel?lular matrix to support 3D architecture has been challenging for high-throughput screening (HTS)-based drug discovery due to technical difficulties. Using genetically engineered human colon organoids as a model system, here we report our effort to minia-turize such 3D organoid culture with extracellular matrix support in high-density plates to enable HTS. We first established orga-noid culturing in a 384-well plate format and validated its application in a cell viability HTS assay by screening a 2036-compound library. We further miniaturized the 3D organoid culturing in a 1536-well ultra-HTS format and demonstrated its robust perfor?mance for large-scale primary compound screening. Our miniaturized organoid culturing method may be adapted to other types of organoids. By leveraging the power of 3D organoid culture in a high-density plate format, we provide a physiologically relevant screening platform to model tumors to accelerate organoid-based research and drug discovery.