机构:[1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, 610065, People's Republic of China四川大学华西医院[2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.[3]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.[4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China.[5]Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China.[6]Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.[7]Sichuan Diya BioTechnology Group Company, Chengdu, 641400, China.[8]Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.[9]Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.深圳市康宁医院深圳医学信息中心[10]Research Institute for Intelligent Wearable Systems, the Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 999077, China.
The in vitro recapitulation of tumor microenvironment is of great interest to preclinical screening of drugs. Compared with culture of cell lines, tumor organ slices can better preserve the complex tumor architecture and phenotypic activity of native cells, but are limited by their exposure to fluid shear and gradual degradation under perfusion culture. Here, we established a decellularized liver matrix (DLM)-GelMA "sandwich" structure and a perfusion-based microfluidic platform to support long-term culture of tumor slices with excellent structural integrity and cell viability over 7 days. The DLM-GelMA was able to secrete cytokines and growth factors while providing shear protection to the tumor slice via the sandwich structure, leading to the preservation of the tumor microenvironment where immune cells (CD3, CD8, CD68), tumor-associated fibroblasts (α-SMA), and extracellular matrix components (collagen I, fibronectin) were well maintained. Furthermore, this chip presented anti-tumor efficacy at cisplatin (20 μM) on tumor patients, demonstrating our platform's efficacy to design patient-specific treatment regimens. Taken together, the successful development of this DLM-GelMA sandwich structure on the chip could faithfully reflect the tumor microenvironment and immune response, accelerating the screening process of drug molecules and providing insights for practical medicine.
基金:
The authors would like to acknowledge the support from the
National Key Research and Development Program of China
(2022YFB3804700, 2022YFA1105200), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYYC21010), Organ-on-a-Chip Innovation Base, Central
Government-Guided Special Project for Local Scientific and
Technological Development in Sichuan Province
(2023ZYD0166), the Chengdu City “Unveiling and Commanding” Science and Technology Project (2024-JB00-00018-GX)
and the Collaborative Research Fund with World-leading Research Groups from the Hong Kong Polytechnic University
(P0039523).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2023]版:
大类|2 区工程技术
小类|1 区生化研究方法1 区分析化学2 区化学:综合2 区仪器仪表2 区纳米科技
最新[2023]版:
大类|2 区工程技术
小类|1 区生化研究方法1 区分析化学2 区化学:综合2 区仪器仪表2 区纳米科技
第一作者:
第一作者机构:[1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, 610065, People's Republic of China[2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.[3]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.[4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China.
共同第一作者:
通讯作者:
通讯机构:[1]Department of Respiratory and Critical Care Medicine, Provincial Clinical Research Center for Respiratory Diseases, West China Hospital, Sichuan University, Chengdu, 610065, People's Republic of China[2]National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.[3]College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.[4]Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China.[5]Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China.[10]Research Institute for Intelligent Wearable Systems, the Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, 999077, China.
推荐引用方式(GB/T 7714):
Hu Wenqi,Bei Ho-Pan,Jiang Hongwei,et al.DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing[J].Lab On A Chip.2024,24(15):3718-3727.doi:10.1039/d4lc00278d.
APA:
Hu Wenqi,Bei Ho-Pan,Jiang Hongwei,Wu Di,Yu Xiaorui...&Wang Shuqi.(2024).DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing.Lab On A Chip,24,(15)
MLA:
Hu Wenqi,et al."DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing".Lab On A Chip 24..15(2024):3718-3727