Microfluidic organoid-slice-on-a-chip system for studying anti-cholangiocarcinoma drug efficacy and hepatorenal toxicity.

IF 6.1 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS
Lab on a Chip Pub Date : 2025-03-28 DOI:10.1039/d4lc00902a
Jie Liu, Guohua Wu, Di Wu, Lin Wu, Chenwei Sun, Wenlong Zhang, Qijun Du, Qinrui Lu, Wenqi Hu, Hongyu Meng, Zhi Luo, Guangzhi Liu, Bangchuan Hu, Haijie Hu, Shuqi Wang
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引用次数: 0

Abstract

Organ-chip technology, in contrast to cell culture and animal models, offers a promising platform for accelerating drug development. However, current chip designs simulate human organ functions and there is a lack of multi-organ chip designs that can simultaneously study drug efficacy and hepatorenal toxicity. Here, we developed a novel microfluidic multi-organ chip that integrated cholangiocarcinoma organoids (CCOs) with recellularized liver slices (RLS) and recellularized kidney slices (RKS), to simultaneously assess anti-cholangiocarcinoma drug efficacy and hepatorenal toxicity. Co-culture of patient-derived CCOs with RLS and RKS was successfully achieved for 7 days under flow conditions with enhanced liver and renal cell functions. Furthermore, an in vitro biomimetic model showed IC50 values of trastuzumab emtansine (T-DM1) of around 6.42 ± 7.34 μg mL-1 in four clinical cases, with one outlier of 77.77 μg mL-1 due to patient variability. Post-treatment, RLS and RKS cell viability remained high at 75.67% and 81.03%, respectively, suggesting low hepatorenal toxicity of T-DM1 for treating cholangiocarcinoma. Our study demonstrates the use of an organoid-slice-on-a-chip (OSOC) platform for personalized drug efficacy and toxicity assessment, particularly aiming at leveraging anticancer drugs for off-label use to save patient lives.

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来源期刊
Lab on a Chip
Lab on a Chip 工程技术-化学综合
CiteScore
11.10
自引率
8.20%
发文量
434
审稿时长
2.6 months
期刊介绍: Lab on a Chip is the premiere journal that publishes cutting-edge research in the field of miniaturization. By their very nature, microfluidic/nanofluidic/miniaturized systems are at the intersection of disciplines, spanning fundamental research to high-end application, which is reflected by the broad readership of the journal. Lab on a Chip publishes two types of papers on original research: full-length research papers and communications. Papers should demonstrate innovations, which can come from technical advancements or applications addressing pressing needs in globally important areas. The journal also publishes Comments, Reviews, and Perspectives.
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