Organotypic Models to Study Human Glioblastoma: Studying the Beast in Its Ecosystem

Pamies, David; Zurich, Marie-Gabrielle; Hartung, Thomas

doi:10.1016/j.isci.2020.101633

Cited by 15 publications

(15 citation statements)

References 117 publications

(180 reference statements)

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“…New technologies in stem cells and cell culturing, such as human 3D organotypic models (where it is possible to obtain myelinated axons) [212][213][214][215], are bringing us closer to the in vivo situation of the human brain and have the potential to replace or reduce the use of in vivo and in vitro rodent models. However, these cell cultures also have limitations and associated challenges [220][221][222][223][224][225][226][227][228][229][230][231][232]. It is therefore important to ensure that the application of these models is fit-for-purpose.…”

Section: Discussionmentioning

confidence: 99%

Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

Chesnut

Hartung

Högberg

et al. 2021

IJMS

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Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential. Myelination is a fundamental process in neurodevelopment that should be included in a DNT testing strategy, but there are very few in vitro models of myelination. Thus, there is a need to establish an in vitro myelination assay for DNT. Here, we summarize the routes of myelin toxicity and the known models to study this particular endpoint.

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Section: Discussionmentioning

confidence: 99%

Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

Chesnut

Hartung

Högberg

et al. 2021

IJMS

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“…Some limiting factors include issues with antibody penetration and laser power of a confocal microscope which makes it difficult to image through the entire depth of an organoid. To overcome this, many groups are making cryosections of the organoids ( Pamies et al, 2020 ), however, with the risk to damage the neurites or cell-cell interactions. Another option is tissue clearing processing which is required to obtain high quality images ( Lallemant et al, 2020 ).…”

Section: Challenges and Opportunities For 3d Brain Modelsmentioning

confidence: 99%

The Future of 3D Brain Cultures in Developmental Neurotoxicity Testing

Högberg

Smirnova

2022

Front. Toxicol.

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Human brain is undoubtedly the most complex organ in the body. Thus, it is difficult to develop adequate and at the same time human relevant test systems and models to cover the aspects of brain homeostasis and even more challenging to address brain development. Animal tests for Developmental Neurotoxicity (DNT) have been devised, but because of complex underlying mechanisms of neural development, and interspecies differences, there are many limitations of animal-based approaches. The high costs, high number of animals used per test and technical difficulties of these tests are prohibitive for routine DNT chemical screening. Therefore, many potential DNT chemicals remain unidentified. New approach methodologies (NAMs) are needed to change this. Experts in the field have recommended the use of a battery of human in vitro tests to be used for the initial prioritization of high-risk environmental chemicals for DNT testing. Microphysiological systems (MPS) of the brain mimic the in vivo counterpart in terms of cellular composition, recapitulation of regional architecture and functionality. These systems amendable to use in a DNT test battery with promising features such as (i) complexity, (ii) closer recapitulation of in vivo response and (iii) possibility to multiplex many assays in one test system, which can increase throughput and predictivity for human health. The resent progress in 3D brain MPS research, advantages, limitations and future perspectives are discussed in this review.

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“…In order to address some of the current gaps of knowledge, innovative experimental approaches have been more recently developed. Patients-derived organoids or organotypic cultures are, for example, 3D in vitro models that reproduce the TME interactions and could be very useful for testing novel drugs or screening the patientspecific response and subsequently choose the proper therapeutic intervention (Pamies et al, 2020). However, due to their complexity, at the moment these types of models are of difficult adaptation to high-throughput screening.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…However, due to their complexity, at the moment these types of models are of difficult adaptation to high-throughput screening. New technologies are also currently aiming at overcoming other limitations, such as the integration of microfluidics or 3D bioprinting of tissue structures to circumvent the lack of a complete vasculature system and the infiltration of peripheral immune components (Li et al, 2020;Pamies et al, 2020).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Old Stars and New Players in the Brain Tumor Microenvironment

Parmigiani

Scalera

Mori

et al. 2021

Front. Cell. Neurosci.

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In recent years, the direct interaction between cancer cells and tumor microenvironment (TME) has emerged as a crucial regulator of tumor growth and a promising therapeutic target. The TME, including the surrounding peritumoral regions, is dynamically modified during tumor progression and in response to therapies. However, the mechanisms regulating the crosstalk between malignant and non-malignant cells are still poorly understood, especially in the case of glioma, an aggressive form of brain tumor. The presence of unique brain-resident cell types, namely neurons and glial cells, and an exceptionally immunosuppressive microenvironment pose additional important challenges to the development of effective treatments targeting the TME. In this review, we provide an overview on the direct and indirect interplay between glioma and neuronal and glial cells, introducing new players and mechanisms that still deserve further investigation. We will focus on the effects of neural activity and glial response in controlling glioma cell behavior and discuss the potential of exploiting these cellular interactions to develop new therapeutic approaches with the aim to preserve proper brain functionality.

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Organotypic Models to Study Human Glioblastoma: Studying the Beast in Its Ecosystem

Cited by 15 publications

References 117 publications

Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

Human Oligodendrocytes and Myelin In Vitro to Evaluate Developmental Neurotoxicity

The Future of 3D Brain Cultures in Developmental Neurotoxicity Testing

Old Stars and New Players in the Brain Tumor Microenvironment

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