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

View Article: PubMed Central - PubMed

ABSTRACT

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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Related in: MedlinePlus

UA cells show similar tumorigenic potential to tumor core-derived cells.(A) Kaplan–Meier survival analysis of tumor cells derived from UA and core samples. There was no significant difference between the mice injected with T1402 UA (n = 4) and tumor core-derived cells (n = 3). All mice injected with T1402, Core or UA, showed neurological symptoms related to tumor growth within 11 weeks (P = 0.153, log-rank test). Mice injected with T1311, a secondary GBM, did not show any neurological symptoms and were sacrificed after 100 days. (B) Representative H&E staining of tumors induced by injecting cells from UA and tumor core that were grown under sphere conditions between P5-P8. Scale bar: 1000 μM.
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f6: UA cells show similar tumorigenic potential to tumor core-derived cells.(A) Kaplan–Meier survival analysis of tumor cells derived from UA and core samples. There was no significant difference between the mice injected with T1402 UA (n = 4) and tumor core-derived cells (n = 3). All mice injected with T1402, Core or UA, showed neurological symptoms related to tumor growth within 11 weeks (P = 0.153, log-rank test). Mice injected with T1311, a secondary GBM, did not show any neurological symptoms and were sacrificed after 100 days. (B) Representative H&E staining of tumors induced by injecting cells from UA and tumor core that were grown under sphere conditions between P5-P8. Scale bar: 1000 μM.

Mentions: To investigate the tumorigenic potential of UA-cells expanded in sphere conditions we used intracranial stereotactic injection of these cells and cells from tumor core biopsies into one hemisphere of immuno-compromised mice. Cells from UA and matched tumor core from two patients were used for transplantation experiments, each transplanted into 3–4 mice. Mice injected with cells from T1402 UA and core biopsy developed neurological symptoms and were sacrificed without significant difference in survival (P = 0.153, log-rank test). On the other hand, mice injected with cells from T1311 UA and core biopsy, a secondary GBM, did not show any neurological symptoms and were sacrificed after 100 days (Fig. 6A). Despite the absence of symptoms, cells from both types of samples were found to give rise to tumors (Fig. 6B).


Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells
UA cells show similar tumorigenic potential to tumor core-derived cells.(A) Kaplan–Meier survival analysis of tumor cells derived from UA and core samples. There was no significant difference between the mice injected with T1402 UA (n = 4) and tumor core-derived cells (n = 3). All mice injected with T1402, Core or UA, showed neurological symptoms related to tumor growth within 11 weeks (P = 0.153, log-rank test). Mice injected with T1311, a secondary GBM, did not show any neurological symptoms and were sacrificed after 100 days. (B) Representative H&E staining of tumors induced by injecting cells from UA and tumor core that were grown under sphere conditions between P5-P8. Scale bar: 1000 μM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015049&req=5

f6: UA cells show similar tumorigenic potential to tumor core-derived cells.(A) Kaplan–Meier survival analysis of tumor cells derived from UA and core samples. There was no significant difference between the mice injected with T1402 UA (n = 4) and tumor core-derived cells (n = 3). All mice injected with T1402, Core or UA, showed neurological symptoms related to tumor growth within 11 weeks (P = 0.153, log-rank test). Mice injected with T1311, a secondary GBM, did not show any neurological symptoms and were sacrificed after 100 days. (B) Representative H&E staining of tumors induced by injecting cells from UA and tumor core that were grown under sphere conditions between P5-P8. Scale bar: 1000 μM.
Mentions: To investigate the tumorigenic potential of UA-cells expanded in sphere conditions we used intracranial stereotactic injection of these cells and cells from tumor core biopsies into one hemisphere of immuno-compromised mice. Cells from UA and matched tumor core from two patients were used for transplantation experiments, each transplanted into 3–4 mice. Mice injected with cells from T1402 UA and core biopsy developed neurological symptoms and were sacrificed without significant difference in survival (P = 0.153, log-rank test). On the other hand, mice injected with cells from T1311 UA and core biopsy, a secondary GBM, did not show any neurological symptoms and were sacrificed after 100 days (Fig. 6A). Despite the absence of symptoms, cells from both types of samples were found to give rise to tumors (Fig. 6B).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus