Advances in 3D culture systems for therapeutic discovery and development in brain cancer

Wanigasekara, Janith; Cullen, Patrick J.; Bourke, Paula; Tiwari, Brijesh K.; Curtin, James F.

doi:10.1016/j.drudis.2022.103426

Cited by 18 publications

(27 citation statements)

References 110 publications

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“…The TME plays a significant role in shaping tumor development, metastasis, angiogenesis, resistance to cytotoxicity, and modulation of immune cells [3, 26, 29]. In 3D cell culture, cells engage in physiological interactions, including cell-cell and cell-ECM interactions.…”

Section: Resultsmentioning

confidence: 99%

“…In 3D cell culture, cells engage in physiological interactions, including cell-cell and cell-ECM interactions. These enable cells to thrive in vitro , replicating the TME found in in vivo GBM conditions [3, 26, 30]. The low attachment plate method was used in this study for the development of in vitro U-251 MG and A431 tumour spheroids and we successfully generated consistent tumor spheres that closely emulate the natural in vivo environment, encompassing shape and cellular responses [30, 31].…”

Section: Resultsmentioning

confidence: 99%

“…Increased vascularization, cell heterogeneity, self-renewing cancer stem cells, and interactions within the tumour-microenvironment (TME) all contribute to GBM progression [3]. 3D tumour spheroids provides more accurate models to explore the association between the TME, tumour reoccurrence, and drug resistance [3]. In 3D tumour spheroids, cell-cell interactions and interactions with the cell-extracellular matrix (ECM) component, enable cells to thrive in vitro in an environment that closely replicates in vivo settings [3].…”

Section: Introductionmentioning

confidence: 99%

“…3D tumour spheroids provides more accurate models to explore the association between the TME, tumour reoccurrence, and drug resistance [3]. In 3D tumour spheroids, cell-cell interactions and interactions with the cell-extracellular matrix (ECM) component, enable cells to thrive in vitro in an environment that closely replicates in vivo settings [3]. Therefore, in this current study, we employed 3D tumour spheroid models to more accurately simulate and investigate the impact of US on human GBM and human epidermoid carcinoma.…”

Section: Introductionmentioning

confidence: 99%

“…Glioblastoma (GBM) is a grade IV glioma in adults, characterized as IDH wild type, according to the fifth edition of the WHO classification and defined from a histology and molecular standpoint [1]. GBM stands out as the most common, aggressive, and lethal primary brain tumor in adults, known for its high vascularity and malignancy, characterised by significant neovascularization and brain parenchymal invasion [2, 3]. Despite multimodal treatments such as maximal surgical resection, radiation, and chemotherapy, glioma recurrence and death rates are significant [4, 5].…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Wanigasekara,

Mondala,

Cullen

et al. 2023

Preprint

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A myriad of biological effects can be stimulated by the ultrasound (US) for the treatment of cancer. The objective of our research was to investigate the effect of ultrasound alone and in combination with the chemotherapeutic drugs such as doxorubicin (DOX) and temozolomide (TMZ) on human glioblastoma (GBM) and the human epidermoid carcinoma cancer 2D and 3D cell cultures. Results indicated that the US 96-probe device could induce tumour sphere cytotoxicity in a dosage- and time-dependent manner, with multiple treatments augmenting this cytotoxic effect. With enhanced cytotoxicity, US decreased tumour sphere growth metabolic activity, disrupted spheroid integrity, and heightened the occurrence of DNA double strand breaks, resulting in damage to tumour spheres and an inability to rebuild tumour spheres after multiple US treatments. The combination of US and TMZ/DOX enhanced the efficiency of treatment for GBM and epidermoid carcinoma by enhancing induced cytotoxicity in 3D tumour spheres compared to 2D monolayer cells, and also by increasing the incubation time, which is the most crucial way to differentiate between the effectiveness of drug treatment with and without US. In conclusion, our data demonstrate that US enhances drug diffusion, uptake, and cytotoxicity using 3D spheroid models when compared with 2D cultures. It also demonstrates the significance of 3D cell culture models in drug delivery and discovery research.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Wanigasekara,

Mondala,

Cullen

et al. 2023

Preprint

Self Cite

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Acquired Temozolomide Resistance Instructs Patterns of Glioblastoma Behavior in Gelatin Hydrogels

Kriuchkovskaia,

Eames,

Riggins

et al. 2024

Adv Healthcare Materials

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Acquired drug resistance in glioblastoma (GBM) presents a major clinical challenge and is a key factor contributing to abysmal prognosis, with less than 15 months median overall survival. Aggressive chemotherapy with the frontline therapeutic, temozolomide (TMZ), ultimately fails to kill residual highly invasive tumor cells after surgical resection and radiotherapy. Here, a 3D engineered model of acquired TMZ resistance is reported using two isogenically matched sets of GBM cell lines encapsulated in gelatin methacrylol hydrogels. Response of TMZ‐resistant versus TMZ‐sensitive GBM cell lines within the gelatin‐based extracellular matrix platform is benchmarked and drug response at physiologically relevant TMZ concentrations is further validated. The changes in drug sensitivity, cell invasion, and matrix‐remodeling cytokine production are shown as the result of acquired TMZ resistance. This platform lays the foundation for future investigations targeting key elements of the GBM tumor microenvironment to combat GBM's devastating impact by advancing the understanding of GBM progression and treatment response to guide the development of novel treatment strategies.

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Synergistic cytotoxicity effect of ultrasound and plasma microbubble in glioblastoma 3D tumor sphere model

Wanigasekara,

Cullen,

Tiwari

et al. 2024

Plasma Processes & Polymers

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The combined application of ultrasound (US) and plasma microbubble (PMB) is a promising technology against glioblastoma (GBM). Here, we determined the effects of US and PMB (alone and combined) on U‐251 MG GBM and A431 epidermoid carcinoma spheroids under different conditions. The synergistic treatment of US‐ and PMB‐induced tumor sphere cell death in a time‐, dose‐, treatment frequency‐, and reactive oxygen species dependent manner, while multiple treatments augmented this effect. Synergistic treatments significantly reduced three‐dimensional GBM spheroid regrowth and cell proliferation while inducing cytotoxicity, spheroid shrinkage, and damage to the tumor microenvironment. PMB‐induced cytotoxicity throughout the tumor sphere, likely via long‐lived reactive oxygen and nitrogen species (H2O2, NO2−, and NO3−) and other reactive species.

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Advances in 3D culture systems for therapeutic discovery and development in brain cancer

Cited by 18 publications

References 110 publications

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Ultrasound-mediated drug diffusion, uptake, and cytotoxicity in glioblastoma 3D tumour sphere model

Acquired Temozolomide Resistance Instructs Patterns of Glioblastoma Behavior in Gelatin Hydrogels

Synergistic cytotoxicity effect of ultrasound and plasma microbubble in glioblastoma 3D tumor sphere model

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