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

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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.

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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All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Kim, S. M., Kang, S-G., Park, N. R., Mok, H. S., Huh, Y., Lee, S. J., Jeun, S. S., Hong, Y. K., Park, C. K., & Lang, F. F. (2011). Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model. Child's Nervous System, 27(6), 911-922. https://doi.org/10.1007/s00381-011-1396-y