Optimized alginate-based 3D printed scaffolds as a model of patient derived breast cancer microenvironments in drug discovery

被引:19
作者
Svanstrom, Andreas [1 ]
Rosendahl, Jennifer [2 ]
Salerno, Simona [1 ]
Leiva, Maria Carmen [1 ]
Gregersson, Pernilla [1 ]
Berglin, Mattias [2 ]
Bogestal, Yalda [2 ]
Lausmaa, Jukka [2 ]
Oko, Asaf [2 ]
Chinga-Carrasco, Gary [3 ]
Petronis, Sarunas [2 ]
Standoft, Simon [2 ]
Stahlberg, Anders [1 ,4 ,5 ]
Hakansson, Joakim [2 ,6 ]
Landberg, Goran [1 ,7 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Sahlgrenska Ctr Canc Res, Inst Biomed,Dept Lab Med, Med Regatan 1F, SE-41390 Gothenburg, Sweden
[2] RISE Res Inst Sweden, Div Mat & Prod, Dept Chem Biomat & Text, Unit Biol Funct, SE-50115 Boras, Sweden
[3] RISE PFI AS, Hogskoleringen 6b, NO-7491 Trondheim, Norway
[4] Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
[5] Sahlgrens Univ Hosp, Dept Clin Genet & Genom, SE-41390 Gothenburg, Sweden
[6] Univ Gothenburg, Inst Biomed, Dept Lab Med, POB 440, SE-40530 Gothenburg, Sweden
[7] Sahlgrens Univ Hosp, Dept Clin Pathol & Genet, SE-41345 Gothenburg, Sweden
基金
瑞典研究理事会;
关键词
3D printed scaffolds (3DPS); patient-derived scaffolds (PDS); breast cancer; microenvironment; drug-screening platform; CELL-CULTURE; EXTRACELLULAR-MATRIX; STEM-CELLS; EXPRESSION; RESISTANCE; PERIOSTIN; 5-FLUOROURACIL; MODULATION; MECHANISMS; ENRICHMENT;
D O I
10.1088/1748-605X/ac0451
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting of a 3D grid containing periostin and hydroxyapatite. Breast cancer cell lines (MCF7 and MDA-MB-231) produced similar phenotypes and gene expression levels of cancer stem cell, epithelial-mesenchymal transition, differentiation and proliferation markers when cultured on 3DPS and PDS, contrasting conventional 2D cultures. Importantly, cells cultured on 3DPS and PDS showed scaffold-specific responses to cytotoxic drugs (doxorubicin and 5-fluorouracil) that were different from 2D cultured cells. In conclusion, the data presented support the use of a tunable alginate-based 3DPS as a tumor model in breast cancer drug discovery.
引用
收藏
页数:16
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