Glioma Spheroids Obtained via Ultrasonic Aspiration Are Viable and Express Stem Cell Markers

Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Andersen, Claus L.; Kristensen, Bjarne Winther

doi:10.1227/neu.0000000000000118

Cited by 22 publications

(25 citation statements)

References 81 publications

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“…One important issue could be that UA samples contain a lot of normal brain cells, and 10–14 days is not enough time to deplete normal cells from the culture. Jensen et al reported this observation in their work19. Thus, using these samples ex vivo to prime antigen presenting cells such as dendritic cells for subsequent activation of T cells might increase the risk of autoimmune diseases.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, some studies have shown that there are live cells in UA samples that can be used for expanding cancer cells in cultures1819. However, these studies have some methodological issues.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it used a monolayer cell culture system with serum or serum free medium on a laminin coated surface, which is different from the classical sphere culture system used here18. The Jensen et al study used UA samples to establish organotypic spheroid cultures which were maintained for 14 days19. Although organotypic spheroid culture has been suggested to preserve different tumor compartments of tumor stroma and cancer stem cells including their cellular connection, blood vessels and macrophages, they have disadvantages such as short life span in culture, (10–15 days), and they contain dead cells and undergo necrosis192425.…”

Section: Discussionmentioning

confidence: 99%

“…The Jensen et al study used UA samples to establish organotypic spheroid cultures which were maintained for 14 days19. Although organotypic spheroid culture has been suggested to preserve different tumor compartments of tumor stroma and cancer stem cells including their cellular connection, blood vessels and macrophages, they have disadvantages such as short life span in culture, (10–15 days), and they contain dead cells and undergo necrosis192425. In our opinion, using UA samples in an organotypic spheroid culture system is unlikely to be a good option for clinical use, especially for vaccine therapy setup or drug target therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Recently it was shown that UA samples contain viable tumorigenic cells and can be used as a source for growing GSCs in serum free conditions supplied with EGF and bFGF growth factors1819. However, a side-by-side comparison of the tumor core and UA samples has not yet been systematically performed.…”

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confidence: 99%

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Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells

Behnan

Stangeland

Langella³

et al. 2016

Sci Rep

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Glioma stem cells (GSCs) are thought to be the source of tumor growth and therapy resistance. To understand the biology of GSCs, and target these tumors therapeutically, we need robust strategies for in vitro expansion of primary GSCs. To date, tumor core biopsies have been the main established source of GSCs. Since these samples are used for diagnostic purposes, the available tissue for cell culture and therapeutic targeting can be limited. In addition, a core biopsy is usually taken from one part of the tumor, thus would be unlikely to represent intra-tumor heterogeneity. To overcome these problems, tissue fragments from all over the tumor can be collected using an ultrasonic aspirator during surgery, thus assembling a “global tumor biopsy”. Usually, this ultrasonic aspirate (UA) sample is considered as biological waste after operations. Here, we show that UA samples offer a large and reliable source of live cells. Similar to core biopsies, UA samples enriched for GSCs that differentiated into neural lineages, showed inter-individual variation of GSC markers, and induced tumors. Molecular profiling showed that UA samples cover tumor heterogeneity better than core biopsies. These results suggest that UA samples can be used to establish large scale cultures for therapeutic applications.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells

Behnan

Stangeland

Langella³

et al. 2016

Sci Rep

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Management and outcome of pediatric brainstem and cerebellar peduncular low-grade gliomas: a retrospective analysis of 62 cases

et al. 2021

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High levels of c-Met is associated with poor prognosis in glioblastoma

et al. 2015

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The tyrosine kinase receptor c-Met has been suggested to be involved in crucial parts of glioma biology like tumor stemness, growth and invasion. The aim of this study was to investigate the prognostic value of c-Met in a population-based glioma patient cohort. Tissue samples from 238 patients with WHO grade I, II, III and IV tumors were analyzed using immunohistochemical staining and advanced image analysis. Strong c-Met expression was found in tumor cells, blood vessels, and peri-necrotic areas. At the subcellular level, c-Met was identified in the cytoplasm and in the cell membrane. Measurements of high c-Met intensity correlated with high WHO grade (p = 0.006) but no association with survival was observed in patients with WHO grade II (p = 0.09) or III (p = 0.17) tumors. High expression of c-Met was associated with shorter overall survival in patients with glioblastoma multiforme (p = 0.03). However the prognostic effect of c-Met in glioblastomas was time-dependent and only observed in patients who survived more than 8.5 months, and not within the first 8.5 months after diagnosis. This was significant in multivariate analysis (HR 1.99, 95 % CI 1.29-3.08, p = 0.002) adjusted for treatment and the clinical variables age (HR 1.01, 95 % CI 0.99-1.03, p = 0.30), performance status (HR 1.34, 95 % CI 1.17-1.53, p < 0.001), and tumor crossing midline (HR 1.28, 95 % CI 0.79-2.07, p = 0.29). In conclusion, this study showed that high levels of c-Met holds unfavorable prognostic value in glioblastomas.

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Glioma Spheroids Obtained via Ultrasonic Aspiration Are Viable and Express Stem Cell Markers

Abstract: Viable organotypic and proliferating spheroids were easily obtained from ultrasonic tissue fragments. The preservation of markers and the establishment of cell lines with tumor-initiating cell properties suggest ultrasonic spheroids as a new tissue resource for glioma research.

Cited by 22 publications

References 81 publications

Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells

Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells

Management and outcome of pediatric brainstem and cerebellar peduncular low-grade gliomas: a retrospective analysis of 62 cases

High levels of c-Met is associated with poor prognosis in glioblastoma

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