A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine

Simon Plummer, Stephanie Wallace, Graeme Ball, Roslyn Lloyd, Paula Schiapparelli, Alfredo Quiñones-Hinojosa, Thomas Hartung, David Pamies

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Abstract

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.

Original languageEnglish (US)
Article number1407
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

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Cite this

Plummer, S., Wallace, S., Ball, G., Lloyd, R., Schiapparelli, P., Quiñones-Hinojosa, A., Hartung, T., & Pamies, D. (2019). A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine. Scientific reports, 9(1), [1407]. https://doi.org/10.1038/s41598-018-38130-0