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

TY - JOUR

T1 - A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine

AU - Plummer, Simon

AU - Wallace, Stephanie

AU - Ball, Graeme

AU - Lloyd, Roslyn

AU - Schiapparelli, Paula

AU - Quiñones-Hinojosa, Alfredo

AU - Hartung, Thomas

AU - Pamies, David

N1 - Supported by NIH grants CA183827 and CA195503.

PY - 2019/2/5

Y1 - 2019/2/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85061124735

U2 - 10.1038/s41598-018-38130-0

DO - 10.1038/s41598-018-38130-0

M3 - Article

C2 - 30723234

SN - 2045-2322

VL - 9

SP - 1

EP - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 1407

ER -