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

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2019
Autor:innen
Plummer, Simon
Wallace, Stephanie
Ball, Graeme
Lloyd, Roslyn
Schiapparelli, Paula
Quiñones-Hinojosa, Alfredo
Pamies, David
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Scientific Reports. 2019, 9(1), 1407. eISSN 2045-2322. Available under: doi: 10.1038/s41598-018-38130-0
Zusammenfassung

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.

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570 Biowissenschaften, Biologie
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ISO 690PLUMMER, Simon, Stephanie WALLACE, Graeme BALL, Roslyn LLOYD, Paula SCHIAPPARELLI, Alfredo QUIÑONES-HINOJOSA, Thomas HARTUNG, David PAMIES, 2019. A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine. In: Scientific Reports. 2019, 9(1), 1407. eISSN 2045-2322. Available under: doi: 10.1038/s41598-018-38130-0
BibTex
@article{Plummer2019-02-05Human-45642,
  year={2019},
  doi={10.1038/s41598-018-38130-0},
  title={A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine},
  number={1},
  volume={9},
  journal={Scientific Reports},
  author={Plummer, Simon and Wallace, Stephanie and Ball, Graeme and Lloyd, Roslyn and Schiapparelli, Paula and Quiñones-Hinojosa, Alfredo and Hartung, Thomas and Pamies, David},
  note={Article Number: 1407}
}
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