Identification of phenotypic neural stem cells in a pediatric astroblastoma.

Department of Neurosurgery, Stanford University, California 94305-5327, USA.
Journal of Neurosurgery (Impact Factor: 3.23). 12/2005; 103(5 Suppl):446-50. DOI: 10.3171/ped.2005.103.5.0446
Source: PubMed

ABSTRACT The goal of this study was to illustrate the findings of a significant subpopulation of cells within a pediatric astroblastoma that have the specific cell surface phenotype found on known human neural stem cells.
Cells with a cell surface marker profile characteristic of human neural stem cells were isolated using fluorescence-activated cell sorting from a mostly nonmitotic astroblastoma removed from the brain of an 11-year-old girl. An unusually high proportion (24%) of the cells were CD133 positive and CD24, CD34, and CD45 negative (CD133(+)CD24(-)CD34(-)CD45(-) cells), the phenotypic antigenic pattern associated with neural stem cells; very few CD133-positive cells were not also CD24, CD34, and CD45 negative. Some cells (12%) were CD34 positive, indicating the presence within the tumor of hematopoietic stem cells. Cells formed cytospheres that resembled neurospheres when seeded into stem cell media and coexpressed beta-tubulin and glial fibrillary acidic protein (GFAP) but did not express the oligodendrocyte marker O4. Cell proliferation was demonstrated by incorporation of bromodeoxyuridine. The cells lost their capacity for self-renewal in vitro after four to six passages, although they continued to coexpress beta-tubulin and GFAP. The cells did not differentiate into neurons or astrocytes when placed in differentiation medium.
Although this astroblastoma contained a high proportion of phenotypic neural stemlike cells, the cells had limited proliferative capacity and multipotency. Their role in astroblastoma formation and growth is unknown.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Astroblastoma is a rare tumor, and thus experience with these lesions is very limited. The prognosis and appropriate treatment is not well understood, as few individual centers have enough experience with astroblastoma to guide treatment recommendations. We performed a systematic comprehensive search of the published English language literature on patients undergoing surgery for astroblastoma to summarize what is known about these tumors, and to provide some framework for future efforts in this area. A total of 62 references met our inclusion criteria, and contained individual patient data on 116 patients with astroblastoma. Determination of overall survival rates was performed using Kaplan-Meier analysis. This analysis suggests that the distribution is bimodal, with a prominent peak in young adulthood. Astroblastomas are generally amenable to complete tumor resection, even when very large, with gross total resection (GTR) achieved in 71/85 (84%) of reported patients, including both 9cm tumors reported. Patients undergoing GTR experienced a significant improvement in survival compared to patients who underwent subtotal resection (STR) (5-year progression-free survival: GTR 83% versus [vs.] STR 55%, log rank p=0.011). Although patients receiving external beam radiotherapy or fractionated three-dimensional conformal radiotherapy (XRT) seemed to have lower survival rates, this was not statistically significant (5-year survival: GTR 94% vs. GTR+XRT 73%, log rank p=0.463). Thus, we have reported the results of a summary of the literature on astroblastomas and have accurately described outcome characteristics using a data set that would be difficult to accumulate at a single center treating this tumor.
    Journal of Clinical Neuroscience 06/2011; 18(6):750-4. DOI:10.1016/j.jocn.2010.11.007 · 1.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neural stem cells (NSCs) are undifferentiated neural cells characterized by their high proliferative potential and the capacity for self-renewal with retention of multipotency. Over the past two decades, there has been a huge effort to identify NSCs morphologically, genetically, and molecular biologically. It is still controversial, however, what bona fide NSCs are. To define and characterize NSCs more systematically, it is crucial to explore novel cell-surface marker molecules of NSCs. In this study, we focused on GD3, a b-series ganglioside that is enriched in the immature brain and the subventricular zone (SVZ) of the postnatal and adult brain, and evaluated the usefulness of GD3 as a cell-surface biomarker for identifying NSCs. We demonstrated that GD3 was expressed in more than 80% of NSCs prepared from embryonic, postnatal, and adult mouse brain tissue by the neurosphere culture method. The percentage of GD3-expressing NSCs in neurospheres was nearly the same as it was in neurospheres derived from embryonic, postnatal, and adult brains but decreased drastically to about 40% after differentiation. GD3(+) cells isolated from embryonic mouse striata, postnatal, and adult mouse SVZs by fluorescence-activated cell sorting with an R24 anti-GD3 monoclonal antibody efficiently generated neurospheres compared with GD3(-) cells. These cells possessed multipotency to differentiate into neurons, astrocytes, and oligodendrocytes. These data indicate that GD3 is a unique and powerful cell-surface biomarker to identify and isolate NSCs.
    Glycobiology 09/2009; 20(1):78-86. DOI:10.1093/glycob/cwp149 · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fibroblast growth factor 1 (FGF1) and FGF2 have been shown to maintain the proliferation, self-renewal and multipotent capacities of neural stem/progenitor cells (NSPCs) in vitro. FGF1 is unique for binding to all known FGF receptors. In this study, we investigated if exogenous EGF and FGF1 could be used in the isolation of NSPCs from embryonic mouse brains. We demonstrated that EGF/FGF1-responsive cells exhibited lower proliferation rate and neurosphere formation efficiency than EGF/FGF2-responsive NSPCs. However, EGF/FGF1-responsive mouse brain cells exhibited better neural differentiation capacities than EGF/FGF2-responsive NSPCs at E11.5. Using F1BGFP reporter, we further demonstrated that F1BGFP+ cells showed similar multipotent capacities to CD133+ NSPCs, and could be induced more efficiently toward neuronal differentiation. Our results suggested that EGF/FGF1-responsive cells from E11.5 mouse brains could self-renew and have better multipotency than EGF/FGF2-responsive NSPCs. Further, CD133+ and F1BGFP+ NSPCs may also represent different subsets of NSPCs during neural development and adult neurogenesis.
    Molecular and Cellular Neuroscience 06/2009; 41(3):348-63. DOI:10.1016/j.mcn.2009.04.010 · 3.73 Impact Factor


Available from
May 31, 2014