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

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.

[1]  Yu Sun,et al.  A microfabricated platform for high-throughput unconfined compression of micropatterned biomaterial arrays. , 2010, Biomaterials.

[2]  Ziyi He,et al.  Study of antioxidant effects on malignant glioma cells by constructing a tumor-microvascular structure on microchip. , 2017, Analytica chimica acta.

[3]  Huadong Liu,et al.  Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder. , 2016, Nature chemical biology.

[4]  Tzong-Shiue Yu,et al.  A restricted cell population propagates glioblastoma growth following chemotherapy , 2012, Nature.

[5]  D. Ingber,et al.  Microfluidic organs-on-chips , 2014, Nature Biotechnology.

[6]  Dao Thi Thuy Nguyen,et al.  Recapitulation of cancer stem cell niches in glioblastoma on 3D microfluidic cell culture devices under gravity-driven perfusion , 2018, Journal of Industrial and Engineering Chemistry.

[7]  Gordana Vunjak-Novakovic,et al.  Human bone perivascular niche-on-a-chip for studying metastatic colonization , 2018, Proceedings of the National Academy of Sciences.

[8]  J. Huse,et al.  Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth. , 2014, Cell stem cell.

[9]  A. Olivi,et al.  Cyclopamine‐Mediated Hedgehog Pathway Inhibition Depletes Stem‐Like Cancer Cells in Glioblastoma , 2007, Stem cells.

[10]  Haifang Li,et al.  In Situ Scatheless Cell Detachment Reveals Correlation between Adhesion Strength and Viability at Single-Cell Resolution. , 2018, Angewandte Chemie.

[11]  Yolanda Schaerli,et al.  Evolution of enzyme catalysts caged in biomimetic gel-shell beads. , 2014, Nature chemistry.

[12]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[13]  A. Levchenko,et al.  Lab-on-a-chip devices as an emerging platform for stem cell biology. , 2010, Lab on a chip.

[14]  B. Kristensen,et al.  CD133+ niches and single cells in glioblastoma have different phenotypes , 2011, Journal of Neuro-Oncology.

[15]  Jin‐Ming Lin,et al.  MoS2-LA-PEI nanocomposite carrier for real-time imaging of ATP metabolism in glioma stem cells co-cultured with endothelial cells on a microfluidic system. , 2018, Biosensors & bioelectronics.

[16]  Georgia Panagiotakos,et al.  Inhibition of Notch Signaling in Glioblastoma Targets Cancer Stem Cells via an Endothelial Cell Intermediate , 2010, Stem cells.

[17]  A. Sonabend,et al.  Inhibition of Sonic Hedgehog and Notch Pathways Enhances Sensitivity of CD133+ Glioma Stem Cells to Temozolomide Therapy , 2011, Molecular medicine.

[18]  Teruo Fujii,et al.  Spatiotemporally controlled delivery of soluble factors for stem cell differentiation. , 2012, Lab on a chip.

[19]  Vincent Noireaux,et al.  Programmable on-chip DNA compartments as artificial cells , 2014, Science.

[20]  Alka A. Potdar,et al.  Profilin-1 Phosphorylation Directs Angiocrine Expression and Glioblastoma Progression through HIF-1α Accumulation , 2014, Nature Cell Biology.

[21]  P. Pandolfi,et al.  PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. , 2008, Genes & development.

[22]  Jin-Ming Lin,et al.  Microfluidic isolation of highly pure embryonic stem cells using feeder-separated co-culture system , 2013, Scientific Reports.

[23]  I. Bayazitov,et al.  A perivascular niche for brain tumor stem cells. , 2007, Cancer cell.

[24]  B. Posner,et al.  Discovery of Tumor-Specific Irreversible Inhibitors of Stearoyl CoA Desaturase , 2016, Nature chemical biology.

[25]  Xuesi Chen,et al.  Selective in vivo metabolic cell-labeling-mediated cancer targeting. , 2017, Nature chemical biology.

[26]  D. Kent,et al.  High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays , 2011, Nature Methods.

[27]  Keith L Black,et al.  Hedgehog Signaling Regulates Brain Tumor‐Initiating Cell Proliferation and Portends Shorter Survival for Patients with PTEN‐Coexpressing Glioblastomas , 2008, Stem cells.

[28]  Haifang Li,et al.  Strategy for signaling molecule detection by using an integrated microfluidic device coupled with mass spectrometry to study cell-to-cell communication. , 2013, Analytical chemistry.