A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance

Brown, J.M.C., Zaben, M. ORCID: https://orcid.org/0000-0002-7446-4532, Ormonde, C., Sharouf, F. ORCID: https://orcid.org/0000-0002-3034-3392, Spencer, R., Bhatt, H., Siebzehnrubl, F.A. ORCID: https://orcid.org/0000-0001-8411-8775 and Gray, W.P. ORCID: https://orcid.org/0000-0001-7595-8887 2023. A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance. Biochemical Pharmacology 208 , 115410. 10.1016/j.bcp.2023.115410

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Abstract

Glioblastoma is among the most lethal cancers, with no known cure. A multitude of therapeutics are being developed or in clinical trials, but currently there are no ways to predict which patient may benefit the most from which drug. Assays that allow prediction of the tumor’s response to anti-cancer drugs may improve clinical decision-making. Here, we present a high-density 3D primary cell culture model for short-term testing from resected glioblastoma tissue that is set up on the day of surgery, established within 7 days and viable for at least 3 weeks. High-density 3D cultures contain tumor and host cells, including microglia, and retain key histopathological characteristics of their parent tumors, including proliferative activity, expression of the marker GFAP, and presence of giant cells. This provides a proof-of-concept that 3D primary cultures may be useful to model tumor heterogeneity. Importantly, we show that high-density 3D cultures can be used to test chemotherapy response within a 2–3-week timeframe and are predictive of patient response to Temozolomide therapy. Thus, primary high-density 3D cultures could be a useful tool for brain cancer research and prediction of therapeutic resistance.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	Elsevier
ISSN:	0006-2952
Funders:	MRC
Date of First Compliant Deposit:	1 February 2023
Date of Acceptance:	3 January 2023
Last Modified:	14 Sep 2024 01:31
URI:	https://orca.cardiff.ac.uk/id/eprint/156432

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