A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment

Cornelison, R. Chase; Yuan, John; Tate, K. M.; Petrosky, A.; Beeghly, Garrett F.; Bloomfield, Mathew; Schwager, Samantha C.; Berr, A. L.; Stine, Caleb A.; Cimini, Daniela; Bafakih, Fahad; Mandell, James W.; Purow, Benjamin; Horton, Bethany J.; Munson, Jennifer M.

doi:10.1038/s41698-022-00290-8

Cited by 10 publications

(7 citation statements)

References 52 publications

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“…resistance (51). However, the triculture models, compared with 2D culture models, provide a physiologically relevant model for assessing cancer cell growth, drug response and therapeutic screening (27,51,52). The present study demonstrated higher drug resistance to raloxifene and doxorubicin in the triculture tissueoids compared with in the 3D monoculture and 2D culture models.…”

Section: Discussionmentioning

confidence: 53%

Establishment of a three‑dimensional triculture model on the novel AXTEX‑4D™ platform

et al. 2022

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Cancer can be fatal if it is not treated in a timely manner; therefore, there is a high demand for more specific oncology drugs. Unfortunately, drugs showing positive responses on a two-dimensional (2D) culture platform do not often show the same effect in clinical trials. Therefore, three-dimensional (3D) culture platforms are garnering attention since they more closely mimic the tumor microenvironment (TME). The TME stimulates metastasis and drug resistance, and serves an essential role in tumor formation. An accurate understanding of tumor-stroma interactions is undoubtedly required to improve the response of patients to therapeutic strategies, and cancer therapeutic strategies that do not account for the stroma are considered inadequate. It should be noted that 3D monoculture systems do not completely mimic the TME since other cells in the 3D culture are missing, such as fibroblast or endothelial cells, which are essential components of the stroma; therefore, it is essential to develop advanced 3D culture systems. The present study aimed to develop a versatile triculture model that mimics the native TME; therefore, it could aid in high-throughput screening of chemotherapeutic drugs against cancer by evaluating their effects on tumor progression and cell cytotoxicity. The present study demonstrated the use of the AXTEX-4D™ platform in developing triculture tissueoids composed of MCF-7, human umbilical vein endothelial cells and MRC5 cells, and compared it with a 3D monoculture model (MCF-7) and a 2D culture model. The triculture model was validated for proliferation, ECM markers and T-cell infiltration by confocal microscopy. Alamar Blue assay demonstrated that triculture tissueoids exhibited higher drug resistance than the other two models, thus demonstrating their use in the screening of oncology drugs.

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Section: Discussionmentioning

confidence: 53%

Establishment of a three‑dimensional triculture model on the novel AXTEX‑4D™ platform

et al. 2022

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“…In addition, molecules including TNF‐α and CCL2 involved in immune response affect the core circadian oscillator 26–28 . Glioma alters the microenvironment to resist immune attack and cytokines and chemokines can be hijacked and then lead to circadian disruption 26,29 …”

Section: Introductionmentioning

confidence: 99%

“… 26 , 27 , 28 Glioma alters the microenvironment to resist immune attack and cytokines and chemokines can be hijacked and then lead to circadian disruption. 26 , 29 …”

Section: Introductionmentioning

confidence: 99%

“…[26][27][28] Glioma alters the microenvironment to resist immune attack and cytokines and chemokines can be hijacked and then lead to circadian disruption. 26,29 Circadian activities associated with cerebrovascular reactivity and brain energy metabolism help to maintain central nerve system homeostasis. 30,31 Cerebral arteries possess a functional circadian clock and exhibit a diurnal rhythm in vasoreactivity to ATP.…”

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confidence: 99%

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Insights about circadian clock in glioma: From molecular pathways to therapeutic drugs

Wang

Chen

2022

CNS Neurosci Ther

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Glioma is characterized as the most aggressive brain tumor that occurred in the central nervous system. The circadian rhythm is an essential cyclic change system generated by the endogenous circadian clock. Current studies found that the circadian clock affects glioma pathophysiology. It is still controversial whether the circadian rhythm disruption is a cause or an effect of tumorigenesis. This review discussed the association between cell cycle and circadian clock and provided a prominent molecular theoretical basis for tumor therapy. We illustrated the external factors affecting the circadian clock including thermodynamics, hypoxia, post‐translation, and microRNA, while the internal characteristics concerning the circadian clock in glioma involve stemness, metabolism, radiotherapy sensitivity, and chemotherapy sensitivity. We also summarized the molecular pathways and the therapeutic drugs involved in the glioma circadian rhythm. There are still many questions in this field waiting for further investigation. The results of glioma chronotherapy in sensitizing radiation therapy and chemotherapy have shown great therapeutic potential in improving clinical outcomes. These findings will help us further understand the characteristics of glioma pathophysiology.

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“…Moreover, these models offer a platform to e ciently test the tumorigenicity of subpopulations of glioma cells in a human host microenvironment, as demonstrated in a recent study that identi ed PTPRZ1 + outer radial glial-like cancer stem cells in GBM(Bhaduri et al, 2020). component 3D model coculturing GSCs, human primary human astrocytes, and immortalized human microglia(Cornelison et al, 2022). These models are useful alternatives to GBM-organoid coculture models particularly in that they include important cell types that are commonly missing in brain organoids.Diffuse Midline Glioma, H3K27M-mutant (DMG) and H3G34Rmutant High-grade Glioma (HGG) DMG…”

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confidence: 99%

Modeling nervous system tumors with human stem cells and organoids

Wang

Duan

2022

Preprint

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Nervous system cancers are the 10th leading cause of death worldwide, many of which are difficult to diagnose and exhibit varying degrees of treatment resistance. The limitations of existing cancer models such as patient-derived xenograft (PDX) models and genetically engineered mouse (GEM) models call for the development of novel preclinical cancer models to more faithfully mimic the patient’s cancer and offer additional insights. Recent advances in human stem cell biology, organoid, and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models: cell-of-origin models, tumor organoids, and 3D multicellular coculture models. In this review, we introduced and compared different human stem cell/organoid-derived models, and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems, including glioblastoma (GBM), H3K27M-mutant Diffuse Midline Glioma (DMG) and H3G34R-mutant High-grade Glioma (HGG), Low-grade Glioma (LGG), Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), Medulloblastoma (MB), Atypical Teratoid/rhabdoid Tumor (AT/RT), and meningioma. We further compared these models with PDX and GEM models, and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.

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A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment

Cited by 10 publications

References 52 publications

Establishment of a three‑dimensional triculture model on the novel AXTEX‑4D™ platform

Establishment of a three‑dimensional triculture model on the novel AXTEX‑4D™ platform

Insights about circadian clock in glioma: From molecular pathways to therapeutic drugs

Modeling nervous system tumors with human stem cells and organoids

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