In vitro biomimetic models for glioblastoma-a promising tool for drug response studies

Stanković, Tijana; Ranđelović, Teodora; Dragoj, Miodrag; Burić, Sonja Stojković; Fernández, Luís; Ochoa, Ignacio; Pérez-Garcı́a, Vı́ctor M.; Pešić, Milica

doi:10.1016/j.drup.2021.100753

Cited by 39 publications

(31 citation statements)

References 295 publications

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“…Recently, several 3D bio-mimicking human glioblastoma cell culture models have been developed. These models that more faithfully reconstitute glioblastoma complexity were successfully used for drug screening [8]. However, until now, there were no 3D glioblastoma cell cultures able to mimic the time frame and duration of treatment cycles typically administered to glioblastoma patients.…”

Section: Discussionmentioning

confidence: 99%

“…We used 100 µM TMZ as IC50 concentration for U87 reported in several studies [27,28]. When compared to 2D glioblastoma cell culture, our 3D culture was more resilient to TMZ thus resembling the response to TMZ in glioblastoma patients [8].…”

Section: Discussionmentioning

confidence: 99%

“…However, 2D models, due to their simplicity, fail to correctly imitate the 3D environment and the important environmental cues, which often leads to unsuccessful and contradictory results [6,7]. Recently, different 3D bio-mimicking human glioblastoma cell culture models have been advanced to more faithfully reconstitute glioblastoma complexity and better mimic its response to therapy [8]. Spheroids are widely used glioblastoma 3D models, which enable high-throughput testing of various therapeutic options with higher reproducibility at an affordable price [9].…”

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing

et al. 2021

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Background: Various three-dimensional (3D) glioblastoma cell culture models have a limited duration of viability. Our aim was to develop a long-term 3D glioblastoma model, which is necessary for reliable drug response studies. Methods: Human U87 glioblastoma cells were cultured in alginate microfibers for 28 days. Cell growth, viability, morphology, and aggregation in 3D culture were monitored by fluorescent and confocal microscopy upon calcein-AM/propidium iodide (CAM/PI) staining every seven days. The glioblastoma 3D model was validated using temozolomide (TMZ) treatments 3 days in a row with a recovery period. Cell viability by MTT and resistance-related gene expression (MGMT and ABCB1) by qPCR were assessed after 28 days. The same TMZ treatment schedule was applied in 2D U87 cell culture for comparison purposes. Results: Within a long-term 3D model system in alginate fibers, U87 cells remained viable for up to 28 days. On day 7, cells formed visible aggregates oriented to the microfiber periphery. TMZ treatment reduced cell growth but increased drug resistance-related gene expression. The latter effect was more pronounced in 3D compared to 2D cell culture. Conclusion: Herein, we described a long-term glioblastoma 3D model system that could be particularly helpful for drug testing and treatment optimization.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing

et al. 2021

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“…A range of 3D hydrogels made up of natural, synthetic, and hybrid polymers have been used to evaluate GBM progression. [213] Hydrogel fabrication routinely involves chemical modification of macromer precursors to suit the application of well-characterized chemical crosslinking strategies such as free-radical initiated photocrosslinking, Michael-type addition, Diels-Alder, and strain promoted azide-alkyne cycloaddition "click" reactions among others, which yield 3D hydrogels that are cytocompatible and possess tunable biophysical properties. [214] The most common materials for 3D cell culture are collagen and Matrigel, which have been widely used to evaluate glioma cell morphology, invasion, proliferation, and stemness.…”

Section: Hydrogel Scaffolds and In Vitro Platform Technologiesmentioning

confidence: 99%

Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma

Tondepu

Karumbaiah

2021

Adv Healthcare Materials

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Glioblastoma (GBM) is a stage IV astrocytoma that carries a dismal survival rate of ≈10 months postdiagnosis and treatment. The highly invasive capacity of GBM and its ability to escape therapeutic challenges are key factors contributing to the poor overall survival rate. While current treatments aim to target the cancer cell itself, they fail to consider the significant role that the GBM tumor microenvironment (TME) plays in promoting tumor progression and therapeutic resistance. The GBM tumor glycocalyx and glycan-rich extracellular matrix (ECM), which are important constituents of the TME have received little attention as therapeutic targets. A wide array of aberrantly modified glycans in the GBM TME mediate tumor growth, invasion, therapeutic resistance, and immunosuppression. Here, an overview of the landscape of aberrant glycan modifications in GBM is provided, and the design and utility of 3D glycomaterials are discussed as a tool to evaluate glycan-mediated GBM progression and therapeutic efficacy. The development of alternative strategies to target glycans in the TME can potentially unveil broader mechanisms of restricting tumor growth and enhancing the efficacy of tumor-targeting therapeutics.

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“…Researchers have found that 3D models are particularly successful in modeling the lineage progression, cellular heterogeneity and invasive potential of these devastating cancers (see Luo and Li, 2021 for a recent review). 3D modeling approaches for glioblastoma are ever evolving and have included organoids generated from primary patient samples or hPSC derivatives, and more recently bioprinted constructs that aim to more faithfully recapitulate multiple elements of the tumor tissue microenvironment (Gimple et al, 2019 ; Zhang et al, 2020 ; Stanković et al, 2021 ). There are two main approaches to 3D cancer modeling: creating a “tumorsphere” consisting of cancer cells to model growth, signaling and drug response (Lenin et al, 2021 ; Pinto et al, 2021 ) or co-culture of cancer cells with “normal” organoids to study invasion and tumor formation (Choe et al, 2020 ; Azzarelli et al, 2021 ).…”

Section: Complementing and Building On Animal Models With Human Stem Cell Modelsmentioning

confidence: 99%

Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells

Knock

Julian

2021

Front. Cell. Neurosci.

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The brain is our most complex and least understood organ. Animal models have long been the most versatile tools available to dissect brain form and function; however, the human brain is highly distinct from that of standard model organisms. In addition to existing models, access to human brain cells and tissues is essential to reach new frontiers in our understanding of the human brain and how to intervene therapeutically in the face of disease or injury. In this review, we discuss current and developing culture models of human neural tissue, outlining advantages over animal models and key challenges that remain to be overcome. Our principal focus is on advances in engineering neural cells and tissue constructs from human pluripotent stem cells (PSCs), though primary human cell and slice culture are also discussed. By highlighting studies that combine animal models and human neural cell culture techniques, we endeavor to demonstrate that clever use of these orthogonal model systems produces more reproducible, physiological, and clinically relevant data than either approach alone. We provide examples across a range of topics in neuroscience research including brain development, injury, and cancer, neurodegenerative diseases, and psychiatric conditions. Finally, as testing of PSC-derived neurons for cell replacement therapy progresses, we touch on the advancements that are needed to make this a clinical mainstay.

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In vitro biomimetic models for glioblastoma-a promising tool for drug response studies

Cited by 39 publications

References 295 publications

Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing

Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing

Glycomaterials to Investigate the Functional Role of Aberrant Glycosylation in Glioblastoma

Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells

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