A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance
A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance
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.
Ormonde C、Spencer R、Bhatt H、Siebzehnrubl FA、Gray WP、Sharouf F、Zaben M、Brown J
Division of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff and Vale University Health Board||B.R.A.I.N Biomedical Research Unit, Cardiff UniversityDivision of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff and Vale University Health Board||Department of Neurosurgery, University Hospital of Wales||B.R.A.I.N Biomedical Research Unit, Cardiff UniversityDepartment of Neurosurgery, University Hospital of WalesSchool of Biosciences, European Cancer Stem Cell Research Institute, CF24 4HQ Cardiff UniversityDivision of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff and Vale University Health Board||Department of Neurosurgery, University Hospital of Wales||B.R.A.I.N Biomedical Research Unit, Cardiff UniversityDivision of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff and Vale University Health Board||Department of Neurosurgery, University Hospital of Wales||B.R.A.I.N Biomedical Research Unit, Cardiff UniversityDivision of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff and Vale University Health Board||Department of Neurosurgery, University Hospital of Wales||B.R.A.I.N Biomedical Research Unit, Cardiff UniversityDivision of Psychological Medicine and Clinical Neurosciences, University Hospital Wales, Cardiff and Vale University Health Board
肿瘤学医学研究方法神经病学、精神病学
in vitropreclinical modelspersonalized medicineprecision medicine
Ormonde C,Spencer R,Bhatt H,Siebzehnrubl FA,Gray WP,Sharouf F,Zaben M,Brown J.A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance[EB/OL].(2025-03-28)[2025-06-08].https://www.medrxiv.org/content/10.1101/2022.10.22.22281352.点此复制
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