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Reconstituting Glioma Perivascular Niches on a Chip for Insights into Chemoresistance of Glioma

Lin, Caihou, Lin, Ling, Mao, Sifeng, Yang, Lijuan, Yi, Linglu, Lin, Xuexia, Wang, Junming, Lin, Zhi-Xiong, Lin, Jin-Ming
Analytical chemistry 2018 v.90 no.17 pp. 10326-10333
coculture, drug therapy, endothelial cells, genes, niches, spectrometers, stem cells
In this work, we report the direct diagnosing chemoresistance of glioma stem cells (GSCs) during chemotherapy on a biomimetric microsystem that reconstitutes glioma perivascular niches on a chip. Glioma stem cells and endothelial cells were specially cocultured onto the biomimetric system to precisely control stem cell coculture for the proof-of-principle studies. The expression levels of 6-O-methylguanine was confirmed by mass spectrometer, and Bmi-1 gene was also investigated to uncover the chemoresistance of GSCs. The results demonstrated that the formation of perivascular niches effectively maintains the glioma stem cells at a pluripotent status owing to their successful cellular interactions. A stronger chemoresistance of glioma stem cells was confirmed by the formation of the GSCs neurosphere, the expression levels of 6-O-methylguanine and Bmi-1 gene. The vital role of endothelial cells in chemoresistance was demonstrated. The chemoresistance reported in this work will contribute to glioma therapy.