Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

作     者：Yancheng Cui Rongrong Xiao Yushi Zhou Jianchuang Liu Yi Wang Xiaodong Yang Zhanlong Shen Bin Liang Kai Shen Yi Li Geng Xiong Yingjiang Ye Xiaoni Ai Yancheng Cui;Rongrong Xiao;Yushi Zhou;Jianchuang Liu;Yi Wang;Xiaodong Yang;Zhanlong Shen;Bin Liang;Kai Shen;Yi Li;Geng Xiong;Yingjiang Ye;Xiaoni Ai

作者机构：State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Gastrointestinal SurgeryPeking University People’s HospitalBeijing 100044China Beijing Daxiang Biotech Co.Ltd.Beijing 100195China Merck Innovation Hub(Guangdong)Co.Ltd.Guangzhou 510005China 

基　　金：supported by grants from the National Natural Science Foundation of China (No.82174086) the Beijing Natural Science Foundation (No.7222273) the Beijing Xisike Clinical Oncology Research Foundation (Nos.Y-xsk2021-0004 and Y-XD202001-0172) the Youth Talents Promotion Project of China Association of Chinese Medicine (No.2020-QNRC2-08) the Clinical Medicine Plus X-Young Scholars Project of Peking University (No.BMU2021MX009) the Peking University People’s Hospital Research and Development Funds (No.RDY2020-18) 

出 版 物：《Bio-Design and Manufacturing》 (生物设计与制造（英文）)

年 卷 期：2022年第5卷第4期

页      码：674-686页

摘      要：The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid(PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z’ factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore,the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.

主 题 词：Organoid on chip Patient-derived organoids Precise oncology Colorectal neoplasm Drug screening 

学科分类：1002[医学-临床医学类] 100214[100214] 10[医学] 

核心收录：

D　O　I：10.1007/s42242-022-00206-2

馆 藏 号：203114596...