期刊
BIOMATERIALS
卷 202, 期 -, 页码 35-44出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.02.024
关键词
Tumor; Glioblastoma; Endothelial; Co-culture; Cancer model; Three-dimensional
资金
- NIH [R01DE024772]
- NSF CAREER award [CBET-1351289]
- California Institute for Regenerative Medicine Tools and Technologies Award [RT3-07804]
- Stanford Child Health Research Institute Faculty Scholar Award
- Stanford Bio-X IIP grant award
- Alliance for Cancer Gene Therapy Young Investigator award grant
- Stanford Chem-H Institute
- Stanford Graduate Fellowship
- Stanford Interdisciplinary Graduate Fellowship
- Stanford Child Health Research Institute postdoctoral fellowship
Glioblastoma (GBM) is an aggressive malignant brain tumor with median survival of 12 months and 5-year survival rate less than 5%. GBM is highly vascularized, and the interactions between tumor and endothelial cells play an important role in driving tumor growth. To study tumor-endothelial interactions, the gold standard co-culture model is transwell culture, which fails to recapitulate the biochemical or physical cues found in tumor niche. Recently, we reported the development of poly(ethylene-glycol)-based hydrogels as 3D niche that supported GBM proliferation and invasion. To further mimic the microanatomical architecture of tumor-endothelial interactions in vivo, here we developed a hydrogel-based co-culture model that mimics the spatial organization of tumor and endothelial cells. To increase the physiological relevance, patient-derived GBM cells and mouse brain endothelial cells were used as model cell types. Using hydrolytically-degradable alginate fibers as porogens, endothelial cells were deployed and patterned into vessel-like structures in 3D hydrogels with high cell viability and retention of endothelial phenotype. Co-culture led to a significant increase in GBM cell proliferation and decrease in endothelial cell expression of cell adhesion proteins. In summary, we have developed a novel 3D coculture model that mimics the in vivo spatial organization of brain tumor and endothelial cells. Such model may provide a valuable tool for future mechanistic studies to elucidate the effects of tumor-endothelial interactions on tumor progression in a more physiologically-relevant manner.
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