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 - http://www.scopus.com/inward/record.url?scp=85061124735&partnerID=8YFLogxK
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 -
