Glioblastoma and cerebral organoids: development and analysis of an <i>in vitro</i> model for glioblastoma migration

Fedorová, Veronika; Pospíšilová, Veronika; Váňová, Tereza; Černá, Kateřina; Abaffy, Pavel; Sedmik, Jiri; Raška, Jan; Vochyánová, Simona; Matusova, Zuzana; Houserová, Jana; Valihrach, Lukás; Hodný, Zdeněk; Bohačiaková, Dáša

doi:10.1002/1878-0261.13389

Cited by 8 publications

(2 citation statements)

References 40 publications

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“…Cerebral organoids were generated using the protocol described previously [73,74]. Briefly, for spheroid formation, cells were plated at day 0 into non-adherent V-shaped 96-well plates at 2000-3000 cells in 150 μl of mTeSR TM 1 medium with 50 μM ROCK inhibitor (S1049, Selleckchem).…”

Section: Methodsmentioning

confidence: 99%

Domino-like Effect of C112R Mutation on ApoE4 Aggregation and Its Reduction by Alzheimer’s Disease Drug Candidate

Nemergut

Marques

Uhrík

et al. 2022

Preprint

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Apolipoprotein 4 (APOE) ϵ4 genotype is the most prevalent risk factor for late-onset Alzheimer's Disease (AD). Although APOE4 differs from its non-pathological APOE3 isoform only by the C112R mutation, the mechanism of its proteinopathy is poorly understood. Here, we combine experimental and computational techniques to uncover a domino-like effect of C112R mutation on APOE4 behavior. We found that C112R substitution in APOE4 induces long-distance (>15 Å) conformational changes leading to the formation of a T-shaped dimeric unit that is geometrically different and more aggregation-prone than the APOE3 structure. AD drug candidate tramiprosate and its metabolite 3-sulfopropanoic acid induce APOE3-like conformational behavior in APOE4 and suppress its aggregation propensity. Analysis of APOE ε4/ε4 cerebral organoids treated with tramiprosate revealed its effect on cholesteryl esters, the storage products of excess cholesterol. Overall, our results connect the APOE4 structure with its aggregation propensity, providing a new druggable target for neurodegeneration and ageing.

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Section: Methodsmentioning

confidence: 99%

Domino-like Effect of C112R Mutation on ApoE4 Aggregation and Its Reduction by Alzheimer’s Disease Drug Candidate

Nemergut

Marques

Uhrík

et al. 2022

Preprint

Self Cite

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show abstract

“…Moreover, this GliCO model enabled the maintenance and recapitulation of the mutation profile of the original tumor, contrary to 2D cultures that tend to lose key molecular aberrations over time [168]. Similarly, Fedorova et al [169] co-cultured brain organoids with GBM spheroids. The resulting GliCO displayed increased cell migration in the brain organoid due to the addition of ECM proteins in the culture.…”

Section: Gbm-brain Organotypic Models (Gboms)mentioning

confidence: 99%

Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues

Slika,

Karimov,

Alimonti

et al. 2023

IJMS

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Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.

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A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single‐cell suspension

Kandra,

Vanova,

Jongen

et al. 2024

Biotechnology Journal

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The development of 3D organoids has provided a valuable tool for studying human tissue and organ development in vitro. Cerebral organoids, in particular, offer a unique platform for investigating neural diseases. However, current methods for generating cerebral organoids suffer from limitations such as labor‐intensive protocols and high heterogeneity among organoids. To address these challenges, we present a microfluidic device designed to automate and streamline the formation and differentiation of cerebral organoids. The device utilizes microwells with two different shapes to promote the formation of a single aggregate per well and incorporates continuous medium flow for optimal nutrient exchange. In silico simulations supported the effectiveness of the microfluidic chip in replicating cellular microenvironments. Our results demonstrate that the microfluidic chip enables uniform growth of cerebral organoids, significantly reducing the hands‐on time required for maintenance. Importantly, the performance of the microfluidic system is comparable to the standard 96‐well plate format even when using half the amount of culture medium, and the resulting organoids exhibit substantially developed neuroepithelial buds and cortical structures. This study highlights the potential of custom‐designed microfluidic technology in improving the efficiency of cerebral organoid culture.

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Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration

Cited by 8 publications

References 40 publications

Domino-like Effect of C112R Mutation on ApoE4 Aggregation and Its Reduction by Alzheimer’s Disease Drug Candidate

Domino-like Effect of C112R Mutation on ApoE4 Aggregation and Its Reduction by Alzheimer’s Disease Drug Candidate

Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues

A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single‐cell suspension

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