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Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model.

 Sang-Mok Kim  ;  Seok-Gu Kang  ;  Na-Ri Park  ;  Hyun-Su Mok  ;  Yong-Min Huh  ;  Su-Jae Lee  ;  Sin-Soo Jeun  ;  Yong-Kil Hong  ;  Chun-Kun Park  ;  Frederick F. Lang 
 CHILDS NERVOUS SYSTEM, Vol.27(6) : 911-922, 2011 
Journal Title
Issue Date
Animals ; Brain Neoplasms/etiology ; Brain Neoplasms/pathology* ; Cell Differentiation/physiology ; Disease Models, Animal* ; Glioma/etiology ; Glioma/pathology* ; Humans ; Male ; Mesenchymal Stromal Cells/pathology* ; Mice ; Mice, Nude ; Stromal Cells/pathology ; Stromal Cells/physiology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays/methods
Glioma ; Mesenchymal stem cells ; Perivascular area ; Pericytes ; Stem cell antigen-1 ; Stroma cells
PURPOSE: High-grade gliomas are closely related to the mesenchymal phenotype which might be explained by unorthodox differentiation of glioma cancer stem cells (gCSCs). We reasoned that other non-neural stem cells, especially mesenchymal stem cells (MSCs), might play a role in expressing mesenchymal phenotype of high-grade gliomas. Thus we hypothesized that cells resembling MSCs exist in glioma specimens. METHODS: We created a mouse (m) orthotopic glioma model using human gCSCs. Single-cell suspensions were isolated from glioma specimens and cultured according to the methods for mMSCs or gliomaspheres. These cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with mMSCs or gCSCs. Glioma stroma (GS)-MSCs were exposed to mesenchymal differentiation conditions. To decide the location of GS-MSCs, sections of orthotopic glioma models were analyzed by immunofluorescent labeling. RESULTS: GS-MSCs were isolated which were morphologically similar to mMSCs. FACS analysis showed that the GS-MSCs had similar surface markers to mMSCs (stem cell antigen-1 [Sca-1](+), CD9(+), CD45(-), CD11b(-), CD31(-), and nerve/glial antigen 2 [NG2](-)). GS-MSCs were capable of mesenchymal differentiation. Immunofluorescent labeling indicated that GS-MSCs are located around blood vessels, are distinct from endothelial cells, and have features that partially overlap with vascular pericytes. CONCLUSIONS: Our results indicate that cells similar to mMSCs exist in glioma specimens. The GS-MSCs might be located around vessels, which suggests that GS-MSCs may provide the mesenchymal elements of the vascular niche. GS-MSCs may represent non-neural stem cells that act as an important source of mesenchymal elements, particularly during the growth of gliomas.
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1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
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