Scalable Culturing of Primary Human Glioblastoma Tumor-Initiating Cells with a Cell-Friendly Culture System

Li, Qiang; Lin, Haishuang; Rauch, Jack; Deleyrolle, Loic P.; Reynolds, Brent A.; Viljoen, Hendrik J.; Zhang, Chi; Gu, Linxia; Wyk, Erika Van; Lei, Yu

doi:10.1038/s41598-018-21927-4

Cited by 30 publications

(34 citation statements)

References 55 publications

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“…In order to address the problem of growing cells in static media, researchers have explored the use of microfluidic systems, in which liquid media can be continually passed through growing cells. One exciting example of the use of fluidic chambers in GBM is the generation of glioma cultures for drug discovery came from a recent report, in which GBM primary cells were cultured in a network of hydrogel tubes with circulating media [96]. Cells were pumped into these tubes in a solution containing several brain specific ECM components, including hyalurlonic acid.…”

Section: Novel Strategies For Gbm Cell Culturementioning

confidence: 99%

Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research

Caragher

Chalmers

Gomez-Roman

2019

Cancers

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Glioblastoma (GBM), the most common and aggressive primary brain tumor in adults, remains one of the least treatable cancers. Current standard of care—combining surgical resection, radiation, and alkylating chemotherapy—results in a median survival of only 15 months. Despite decades of investment and research into the development of new therapies, most candidate anti-glioma compounds fail to translate into effective treatments in clinical trials. One key issue underlying this failure of therapies that work in pre-clinical models to generate meaningful improvement in human patients is the profound mismatch between drug discovery systems—cell cultures and mouse models—and the actual tumors they are supposed to imitate. Indeed, current strategies that evaluate the effects of novel treatments on GBM cells in vitro fail to account for a wide range of factors known to influence tumor growth. These include secreted factors, the brain’s unique extracellular matrix, circulatory structures, the presence of non-tumor brain cells, and nutrient sources available for tumor metabolism. While mouse models provide a more realistic testing ground for potential therapies, they still fail to account for the full complexity of tumor-microenvironment interactions, as well as the role of the immune system. Based on the limitations of current models, researchers have begun to develop and implement novel culture systems that better recapitulate the complex reality of brain tumors growing in situ. A rise in the use of patient derived cells, creative combinations of added growth factors and supplements, may provide a more effective proving ground for the development of novel therapies. This review will summarize and analyze these exciting developments in 3D culturing systems. Special attention will be paid to how they enhance the design and identification of compounds that increase the efficacy of radiotherapy, a bedrock of GBM treatment.

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Section: Novel Strategies For Gbm Cell Culturementioning

confidence: 99%

Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research

Caragher

Chalmers

Gomez-Roman

2019

Cancers

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“…Recently, a 3D model based on polystyrene scaffold has been used to predict drug-radiation combination for glioblastoma [ 15 ]. Furthermore, glioblastoma tumour-initiating cells have been successfully maintained in a microscale alginate hydrogel tubes (or AlgTubes) that allows affordable cost for drug discovery [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

A novel 3D in vitro model of glioblastoma reveals resistance to temozolomide which was potentiated by hypoxia

Musah-Eroje

Watson

2019

J Neurooncol

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Purpose Glioblastoma (GBM) is the most common invasive malignant brain tumour in adults. It is traditionally investigated in vitro by culturing cells as a monolayer (2D culture) or as neurospheres (clusters enriched in cancer stem cells) but neither system accurately reflects the complexity of the three-dimensional (3D) chemoresistant microenvironment of GBM. Materials and methods Using three GBM cell-lines (U87, U251, and SNB19), the effect of culturing cells in a Cultrex-based basement membrane extract (BME) [3D Tumour Growth Assay (TGA)] on morphology, gene expression, metabolism, and temozolomide chemoresistance was investigated. Results Cells were easily harvested from the 3D model and cultured as a monolayer (2D) and neurospheres. Indeed, the SNB19 cells formed neurospheres only after they were first cultured in the 3D model. The expression of CD133 and OCT4 was upregulated in the neurosphere and 3D assays respectively. Compared with cells cultured in the 2D model, cells were more resistant to temozolomide in the 3D model and this resistance was potentiated by hypoxia. Conclusion Taken together, these results suggest that micro-environmental factors influence GBM sensitivity to temozolomide. Knowledge of the mechanisms involved in temozolomide resistance in this 3D model might lead to the identification of new strategies that enable the more effective use of the current standard of care agents. Electronic supplementary material The online version of this article (10.1007/s11060-019-03107-0) contains supplementary material, which is available to authorized users.

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“…To address the challenge, we previously developed a scalable and high-yield cell culture method for expanding hPSCs and other human cells (Li et al., 2018a, Li et al., 2018b, Lin et al., 2018a, Lin et al., 2018b). With this method, cells are processed into microscale alginate hydrogel tubes (AlgTubes) that are suspended in the cell culture medium.…”

Section: Introductionmentioning

confidence: 99%

Engineered Microenvironment for Manufacturing Human Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells

Lin

Qiu

et al. 2019

Stem Cell Reports

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SummaryHuman pluripotent stem cell-derived vascular smooth muscle cells (hPSC-VSMCs) are of great value for disease modeling, drug screening, cell therapies, and tissue engineering. However, producing a high quantity of hPSC-VSMCs with current cell culture technologies remains very challenging. Here, we report a scalable method for manufacturing hPSC-VSMCs in alginate hydrogel microtubes (i.e., AlgTubes), which protect cells from hydrodynamic stresses and limit cell mass to <400 μm to ensure efficient mass transport. The tubes provide cells a friendly microenvironment, leading to extremely high culture efficiency. We have shown that hPSC-VSMCs can be generated in 10 days with high viability, high purity, and high yield (∼5.0 × 108 cells/mL). Phenotype and gene expression showed that VSMCs made in AlgTubes and VSMCs made in 2D cultures were similar overall. However, AlgTube-VSMCs had higher expression of genes related to vasculature development and angiogenesis, and 2D-VSMCs had higher expression of genes related to cell death and biosynthetic processes.

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Scalable Culturing of Primary Human Glioblastoma Tumor-Initiating Cells with a Cell-Friendly Culture System

Cited by 30 publications

References 55 publications

Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research

Glioblastoma’s Next Top Model: Novel Culture Systems for Brain Cancer Radiotherapy Research

A novel 3D in vitro model of glioblastoma reveals resistance to temozolomide which was potentiated by hypoxia

Engineered Microenvironment for Manufacturing Human Pluripotent Stem Cell-Derived Vascular Smooth Muscle Cells

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