Practical Review on Preclinical Human 3D Glioblastoma Models: Advances and Challenges for Clinical Translation

Soubéran, Aurélie; Tchoghandjian, Aurélie

doi:10.3390/cancers12092347

Cited by 31 publications

(40 citation statements)

References 114 publications

(223 reference statements)

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“…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]. Next to the spheroid, various scaffold-based 3D glioblastoma models were developed with the intention to mimic interactions between cancer cells and the extracellular matrix (ECM) [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…Spheroids are widely used glioblastoma 3D models, which enable high-throughput testing of various therapeutic options with higher reproducibility at an affordable price [9]. Next to the spheroid, various scaffold-based 3D glioblastoma models were developed with the intention to mimic interactions between cancer cells and the extracellular matrix (ECM) [9,10]. Among them, alginate is one of the most commonly used polymers for microencapsulation and the development of scaffold-based 3D cell cultures.…”

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: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…In vitro, glioblastoma cells can also be cultivated as 3D spheroids or organoids [ 165 , 166 , 167 , 178 ]. As in 2D cultures, the tumor-surrounding microenvironment is absent.…”

Section: Preclinical Models To Study Glutamate Interaction and Tumor-mentioning

confidence: 99%

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

Lange

Hörnschemeyer

Kirschstein

2021

Cells

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The progression of glioblastomas is associated with a variety of neurological impairments, such as tumor-related epileptic seizures. Seizures are not only a common comorbidity of glioblastoma but often an initial clinical symptom of this cancer entity. Both, glioblastoma and tumor-associated epilepsy are closely linked to one another through several pathophysiological mechanisms, with the neurotransmitter glutamate playing a key role. Glutamate interacts with its ionotropic and metabotropic receptors to promote both tumor progression and excitotoxicity. In this review, based on its physiological functions, our current understanding of glutamate receptors and glutamatergic signaling will be discussed in detail. Furthermore, preclinical models to study glutamatergic interactions between glioma cells and the tumor-surrounding microenvironment will be presented. Finally, current studies addressing glutamate receptors in glioma and tumor-related epilepsy will be highlighted and future approaches to interfere with the glutamatergic network are discussed.

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“…However, it may be useful in the future to develop media containing the relevant supplements and growth factors, as this has previously been demonstrated to improve the metabolic fidelity and biological relevance for in vitro models [ 22 ]. Organoids which maintain the morphological and histological features of the original tumour have been developed to establish and culture PDOs from many common tumour types, including glioblastoma [ 23 ], breast [ 24 ], pancreas [ 25 ], prostate [ 26 , 27 ], liver [ 28 ], lung [ 4 , 29 ] and colon [ 30 ], with varying degrees of success and reproducibility.…”

Section: Establishment Of Organoidsmentioning

confidence: 99%

Patient-Derived Organoids as a Model for Cancer Drug Discovery

Rae

Amato

Braconi

2021

IJMS

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In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.

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Practical Review on Preclinical Human 3D Glioblastoma Models: Advances and Challenges for Clinical Translation

Cited by 31 publications

References 114 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

Glutamatergic Mechanisms in Glioblastoma and Tumor-Associated Epilepsy

Patient-Derived Organoids as a Model for Cancer Drug Discovery

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