Micro‐Engineered Organoid‐on‐a‐Chip Based on Mesenchymal Stromal Cells to Predict Immunotherapy Responses of HCC Patients
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Published:2023-07-23
Issue:27
Volume:10
Page:
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ISSN:2198-3844
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Container-title:Advanced Science
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language:en
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Short-container-title:Advanced Science
Author:
Zou Zhengyu1ORCID,
Lin Zhun2,
Wu Chenglin3,
Tan Jizhou3,
Zhang Jie2,
Peng Yanwen4,
Zhang Kunsong3,
Li Jiaping3,
Wu Minhao1ORCID,
Zhang Yuanqing2ORCID
Affiliation:
1. Zhongshan School of Medicine Sun Yat‐sen University Guangzhou 510080 China
2. School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 China
3. The First Affiliated Hospital Sun Yat‐sen University Guangzhou 510080 China
4. The Third Affiliated Hospital Sun Yat‐sen University Guangzhou 510635 China
Abstract
AbstractHepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Patient‐derived organoid (PDO) has great potential in precision oncology, but low success rate, time‐consuming culture, and lack of tumor microenvironment (TME) limit its application. Mesenchymal stromal cells (MSC) accumulate in primary site to support tumor growth and recruit immune cells to form TME. Here, MSC and peripheral blood mononuclear cells (PBMC) coculture is used to construct HCC organoid‐on‐a‐chip mimicking original TME and provide a high‐throughput drug‐screening platform to predict outcomes of anti‐HCC immunotherapies. HCC‐PDOs and PBMC are co‐cultured with MSC and Cancer‐associated fibroblasts (CAF). MSC increases success rate of biopsy‐derived PDO culture, accelerates PDO growth, and promotes monocyte survival and differentiation into tumor‐associated macrophages. A multi‐layer microfluidic chip is designed to achieve high‐throughput co‐culture for drug screening. Compared to conventional PDOs, MSC‐PDO‐PBMC and CAF‐PDO‐PBMC models show comparable responses to chemotherapeutic or targeted anti‐tumor drugs but more precise prediction potential in assessing patients’ responses to anti‐PD‐L1 drugs. Moreover, this microfluidic platform shortens PDO growth time and improves dimensional uniformity of organoids. In conclusion, the study successfully constructs microengineered organoid‐on‐a‐chip to mimic TME for high‐throughput drug screening, providing novel platform to predict immunotherapy response of HCC patients.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
China Postdoctoral Science Foundation
Fundamental Research Funds for the Central Universities
Higher Education Discipline Innovation Project
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)