An orthotopic glioblastoma animal model suitable for high-throughput screenings

Neuro-oncology
Linda PudelkoLars Bräutigam

Abstract

Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies, and clinically relevant orthotopic zebrafish models have been developed. However, currently available GBM orthotopic zebrafish models do not support high-throughput drug discovery screens. We transplanted both GBM cell lines as well as patient-derived material into zebrafish blastulas. We followed the behavior of the transplants with time-lapse microscopy and real-time in vivo light-sheet microscopy. We found that GBM material transplanted into zebrafish blastomeres robustly migrated into the developing nervous system, establishing an orthotopic intracranial tumor already 24 hours after transplantation. Detailed analysis revealed that our model faithfully recapitulates the human disease. We have developed a robust, fast, and automatable transplantation assay to establish orthotopic GBM tumors in zebrafish. In contrast to c...Continue Reading

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Citations

Jan 11, 2020·Cell Death and Differentiation·Ishani DasUlrika Warpman Berglund
Sep 15, 2019·Disease Models & Mechanisms·Faye L RobertsonSteven M Pollard
Oct 3, 2019·Cells·Cintia Carla da HoraBakhos A Tannous
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Kelly Z MiaoHui Feng
Aug 8, 2021·Nanomaterials·Alba Pensado-LópezFernando Torres Andón
Dec 3, 2021·Expert Reviews in Molecular Medicine·Peng LiuAnke Brüning-Richardson

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