A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine.
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5 février 2019
- doi: 10.1038/s41598-018-38130-0
- issn: 2045-2322
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info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-018-38130-0
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info:eu-repo/semantics/altIdentifier/pmid/30723234
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info:eu-repo/semantics/altIdentifier/eissn/2045-2322
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_968C606B3D563
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
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S. Plummer et al., « A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine. », Serveur académique Lausannois, ID : 10.1038/s41598-018-38130-0
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Résumé
A high throughput histology (microTMA) platform was applied for testing drugs against tumors in a novel 3D heterotypic glioblastoma brain sphere (gBS) model consisting of glioblastoma tumor cells, iPSC-derived neurons, glial cells and astrocytes grown in a spheroid. The differential responses of gBS tumors and normal neuronal cells to sustained treatments with anti-cancer drugs temozolomide (TMZ) and doxorubicin (DOX) were investigated. gBS were exposed to TMZ or DOX over a 7-day period. Untreated gBS tumors increased in size over a 4-week culture period, however, there was no increase in the number of normal neuronal cells. TMZ (100 uM) and DOX (0.3 uM) treatments caused ~30% (P~0.07) and ~80% (P < 0.001) decreases in the size of the tumors, respectively. Neither treatment altered the number of normal neuronal cells in the model. The anti-tumor effects of TMZ and DOX were mediated in part by selective induction of apoptosis. This platform provides a novel approach for screening new anti-glioblastoma agents and evaluating different treatment options for a given patient.