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

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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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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0071299 and 2010-0004506) and a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (1020340).

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Authors and Affiliations

  1. Department of Neurosurgery, The Catholic University of Korea College of Medicine, Seoul St. Mary’s Hospital, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

    Sang-Mok Kim, Seok-Gu Kang, Na-Ri Park, Sin-Soo Jeun, Yong-Kil Hong & Chun-Kun Park

  2. Department of Neurosurgery, The Catholic University of Korea College of Medicine, Uijeongbu St. Mary’s Hospital, 65-1 Kumoh-dong, Uijeongbu, 480-717, South Korea

    Hyun-Su Mok

  3. Department of Radiology, College of Medicine, Yonsei University, 134 Sinchon-dong, Seodaemun-gu, Seoul, 120-752, South Korea

    Yong-Min Huh

  4. Department of Chemistry, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, South Korea

    Su-Jae Lee

  5. Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030-4009, USA

    Frederick F. Lang

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  1. Sang-Mok Kim
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Correspondence to Seok-Gu Kang.

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Kim, SM., Kang, SG., Park, NR. et al. Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model. Childs Nerv Syst 27, 911–922 (2011). https://doi.org/10.1007/s00381-011-1396-y

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  • DOI: https://doi.org/10.1007/s00381-011-1396-y

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