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71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

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A novel glioblastoma invasion model using human brain slice cultures

Ein neuartiges Glioblastom-Invasionsmodell unter Verwendung menschlicher Hirnschnittkulturen

Meeting Abstract

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  • presenting/speaker Vidhya M. Ravi - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
  • Kevin Joseph - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
  • Nicolas Neidert - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
  • Jürgen Beck - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
  • Ulrich G. Hofmann - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
  • Oliver Schnell - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland
  • Dieter Henrik Heiland - Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocP142

doi: 10.3205/20dgnc426, urn:nbn:de:0183-20dgnc4262

Published: June 26, 2020

© 2020 Ravi et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Objective: Over the past several decades, therapies to combat malignant glioma that appeared promising in mice models have failed during clinical trials amongst others due to the differences encountered during translation of research from model organisms to humans. To partially mitigate these difficulties in translation, we present a human cortical organotypic culture based GBM model, which allows us to manipulate individual components of the tumour environment in order to investigate the influence of different cell types in the immunosuppressive tumour microenvironment.

Methods: Human neocortical tissue (at least 2 cm away from the tumour core) or entry cortex from epilepsy surgery, was cultured for up to 21 days post resection using advanced culture conditions. The cultured tissue was further injected with patient derived human GBM cells to create an ex vivo human model of glioblastoma. The role of astrocytes in tumour microenvironment was studied using a microglia loss of function model. Tumour growth was monitored using fluorescence microscopy and microglia crosstalk was studied using flow cytometry and RNA-sequencing analysis.

Results: Our data corroborate differences between astrocytes in human and murine models in different reactive states, showing that the glioblastoma microenvironment is difficult to be accurately modelled using murine models. Results from microglia depletion showed ample evidence of crosstalk between GBM cells, astrocytes and microglia showing the increased intensity of anti-inflammatory cytokine IL-10 and TGFb when microglial depletion was carried out.

Conclusion: This model therefore has potential applications to the fields of neuroscience, neuro-oncology and pharmacotherapy.