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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.

No MeSH data available.


Related in: MedlinePlus

UA- and tumor core-derived cells have similar tumor invasion patterns in vivo.(A,B) A fluorescent overview image and zoom in field of a tumor induced by T1402 and T1311 UA- and tumor core-derived cells. Tissue sections were stained with human-specific Nestin (green) and DAPI. Both UA- and tumor core-derived cells of T1402 formed large tumors that infiltrated into the opposite hemisphere (A). While T1311 induced less invasive tumor cells that were dispersed within the same injection side. (B), Scale bar: 500 μM in overview images and 100 μM in zoom in. (C) A fluorescent image of tumors induced by UA- and tumor core-derived cells showing the angiogenesis in the tumor. Tissue sections were stained with CD31 (red), and αSMA (green) antibodies highlighting the blood vessels. Scale bar 100 μM.
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f7: UA- and tumor core-derived cells have similar tumor invasion patterns in vivo.(A,B) A fluorescent overview image and zoom in field of a tumor induced by T1402 and T1311 UA- and tumor core-derived cells. Tissue sections were stained with human-specific Nestin (green) and DAPI. Both UA- and tumor core-derived cells of T1402 formed large tumors that infiltrated into the opposite hemisphere (A). While T1311 induced less invasive tumor cells that were dispersed within the same injection side. (B), Scale bar: 500 μM in overview images and 100 μM in zoom in. (C) A fluorescent image of tumors induced by UA- and tumor core-derived cells showing the angiogenesis in the tumor. Tissue sections were stained with CD31 (red), and αSMA (green) antibodies highlighting the blood vessels. Scale bar 100 μM.

Mentions: Human-specific Nestin staining indicated that T1402UA and its corresponding core formed large invasive tumors that crossed into the opposite hemispheres (Fig. 7A), while T1311 gave rise to a small number of cells dispersed in hemisphere of the injection site (Fig. 7B). Angiogenesis was detected in T1402 UA- and core-induced tumors, but not those of T1311 (Figs 6B and 7C). Thus, cells from both UA and tumor core samples, expanded under sphere culture condition, showed similar tumorigenic potential. They both form highly invasive tumors or non-invasive tumors that mimic their parental tumor.


Ultrasonic Surgical Aspirate is a Reliable Source For Culturing Glioblastoma Stem Cells
UA- and tumor core-derived cells have similar tumor invasion patterns in vivo.(A,B) A fluorescent overview image and zoom in field of a tumor induced by T1402 and T1311 UA- and tumor core-derived cells. Tissue sections were stained with human-specific Nestin (green) and DAPI. Both UA- and tumor core-derived cells of T1402 formed large tumors that infiltrated into the opposite hemisphere (A). While T1311 induced less invasive tumor cells that were dispersed within the same injection side. (B), Scale bar: 500 μM in overview images and 100 μM in zoom in. (C) A fluorescent image of tumors induced by UA- and tumor core-derived cells showing the angiogenesis in the tumor. Tissue sections were stained with CD31 (red), and αSMA (green) antibodies highlighting the blood vessels. Scale bar 100 μM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: UA- and tumor core-derived cells have similar tumor invasion patterns in vivo.(A,B) A fluorescent overview image and zoom in field of a tumor induced by T1402 and T1311 UA- and tumor core-derived cells. Tissue sections were stained with human-specific Nestin (green) and DAPI. Both UA- and tumor core-derived cells of T1402 formed large tumors that infiltrated into the opposite hemisphere (A). While T1311 induced less invasive tumor cells that were dispersed within the same injection side. (B), Scale bar: 500 μM in overview images and 100 μM in zoom in. (C) A fluorescent image of tumors induced by UA- and tumor core-derived cells showing the angiogenesis in the tumor. Tissue sections were stained with CD31 (red), and αSMA (green) antibodies highlighting the blood vessels. Scale bar 100 μM.
Mentions: Human-specific Nestin staining indicated that T1402UA and its corresponding core formed large invasive tumors that crossed into the opposite hemispheres (Fig. 7A), while T1311 gave rise to a small number of cells dispersed in hemisphere of the injection site (Fig. 7B). Angiogenesis was detected in T1402 UA- and core-induced tumors, but not those of T1311 (Figs 6B and 7C). Thus, cells from both UA and tumor core samples, expanded under sphere culture condition, showed similar tumorigenic potential. They both form highly invasive tumors or non-invasive tumors that mimic their parental tumor.

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