DLM–GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing,Lab on a Chip

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DLM–GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing
Lab on a Chip ( IF 6.1 ) Pub Date : 2024-06-24 , DOI: 10.1039/d4lc00278d
Wenqi Hu _{1,

2,

3,

4} , Ho-Pan Bei ₅ , Hongwei Jiang ₆ , Di Wu _{1,

2,

3,

4} , Xiaorui Yu _{1,

2,

3,

4} , Xintong Zhou ₅ , Qiuwan Sun ₇ , Qinrui Lu ₇ , Qijun Du _{1,

2,

3,

4} , Liangwen Wang ₈ , Zhi Luo ₉ , Guohua Wu ₆ , Xin Zhao _{5,

10} , Shuqi Wang _{1,

2,

3,

4}

Affiliation

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.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610065, China.
College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu, 641400, China.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, 999077, China.
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.
Sichuan Diya BioTechnology Group Company, Chengdu, 641400, China.
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, China.
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.

中文翻译：

DLM-GelMA/肿瘤切片三明治结构芯片上的肿瘤用于药效测试

肿瘤微环境的体外重现对于药物的临床前筛选具有重要意义。与细胞系培养相比，肿瘤器官切片可以更好地保留天然细胞的复杂肿瘤结构和表型活性，但受到其暴露于流体剪切和灌注培养下逐渐降解的限制。在这里，我们建立了脱细胞肝基质（DLM）-GelMA“三明治”结构和基于灌注的微流体平台，以支持肿瘤切片的长期培养，具有优异的结构完整性和细胞活力超过7天。 DLM-GelMA 能够分泌细胞因子和生长因子，同时通过夹层结构为肿瘤切片提供剪切保护，从而保护肿瘤微环境，其中免疫细胞（CD3、CD8、CD68）、肿瘤相关成纤维细胞（α -SMA）和细胞外基质成分（胶原蛋白 I、纤连蛋白）保持良好。此外，该芯片在顺铂 (20 μM) 下对肿瘤患者具有抗肿瘤功效，证明了我们的平台设计患者特异性治疗方案的功效。综上所述，芯片上这种DLM-GelMA三明治结构的成功开发可以忠实地反映肿瘤微环境和免疫反应，加速药物分子的筛选过程，为实用医学提供见解。

更新日期：2024-06-24

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