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, yongmin Huh, Su Jae Lee, Sin Soo Jeun, Yong Kil Hong, Chun Kun Park, Frederick F. Lang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 expresssing 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.

Original languageEnglish
Pages (from-to)911-922
Number of pages12
JournalChild's Nervous System
Volume27
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1

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Mesenchymal Stromal Cells
Glioma
Neoplastic Stem Cells
Blood Vessels
Stem Cells
CD9 Antigen
Flow Cytometry
Phenotype
Pericytes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Kim, Sang Mok ; Kang, Seok-Gu ; Park, Na Ri ; Mok, Hyun Su ; Huh, yongmin ; Lee, Su Jae ; Jeun, Sin Soo ; Hong, Yong Kil ; Park, Chun Kun ; Lang, Frederick F. / Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model. In: Child's Nervous System. 2011 ; Vol. 27, No. 6. pp. 911-922.
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abstract = "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 expresssing 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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Kim, SM, Kang, S-G, Park, NR, Mok, HS, Huh, Y, Lee, SJ, Jeun, SS, Hong, YK, Park, CK & Lang, FF 2011, 'Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model', Child's Nervous System, vol. 27, no. 6, pp. 911-922. https://doi.org/10.1007/s00381-011-1396-y

Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model. / Kim, Sang Mok; Kang, Seok-Gu; Park, Na Ri; Mok, Hyun Su; Huh, yongmin; Lee, Su Jae; Jeun, Sin Soo; Hong, Yong Kil; Park, Chun Kun; Lang, Frederick F.

In: Child's Nervous System, Vol. 27, No. 6, 01.06.2011, p. 911-922.

Research output: Contribution to journalArticle

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T1 - Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model

AU - Kim, Sang Mok

AU - Kang, Seok-Gu

AU - Park, Na Ri

AU - Mok, Hyun Su

AU - Huh, yongmin

AU - Lee, Su Jae

AU - Jeun, Sin Soo

AU - Hong, Yong Kil

AU - Park, Chun Kun

AU - Lang, Frederick F.

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N2 - 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 expresssing 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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