title: Presence of glioma stroma mesenchymal stem cells in a murine orthotopic glioma model.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Kim
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Park
authors.forename: Hyun-Su
authors.initials: HS
authors.lastname: Mok
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sin-Soo
authors.initials: SS
authors.lastname: Jeun
authors.forename: Yong-Kil
authors.initials: YK
authors.lastname: Hong
authors.forename: Chun-Kun
authors.initials: CK
authors.lastname: Park
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000209:etiology / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D005910:Glioma / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods