Identification of phenotypic neural stem cells in a pediatric astroblastoma

Department of Neurosurgery, Stanford University, California 94305-5327, USA.
Journal of Neurosurgery (Impact Factor: 3.74). 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.

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Available from: Yun C. Yung, Sep 25, 2015
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    • "Those marker molecules, however, are intracellular proteins or transcription factors not suitable for isolating native NSCs by fluorescence-activated cell sorting (FACS). Although CD133 (prominin-1) and stage-specific antigen-1 (SSEA-1) localized on the cell surface have been used to isolate NSCs (Uchida et al. 2000; Capela and Temple 2002), those antigens are expressed not only in NSCs but also in other somatic stem cells, cancer stem cells, and embryonic stem cells (Muramatsu and Muramatsu 2004; Huhn et al. 2005; Tong et al. 2008). Moreover, it has been reported that CD133 + /SSEA-1 + and CD133 + /SSEA-1 − cells derived from embryonic stem cells formed neurospheres, floating aggregates of NSCs, at similar frequencies (Peh et al. 2009). "
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    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 · 3.15 Impact Factor
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    • "4. IDENTIFICATION OF BRAIN TUMOUR STEM CELLS If NSCs can be isolated from the brain by culturing serum free in epidermal growth factor (EGF)/fibroblast growth factor (FGF), could this culture system also identify stem cells in brain tumours? Several groups studying human brain tumours identified small numbers of cells with clonogenic potential based on the neurosphere assay (Ignatova et al. 2002; Hemmati et al. 2003; Singh et al. 2003, 2004b; Galli et al. 2004; Yuan et al. 2004; Huhn et al. 2005). In culture, these brain tumour cells form self-renewing neurosphere-like colonies, and they have an ability to differentiate into one or more neural lineages. "
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    ABSTRACT: Conceptual and technical advances in neural stem cell biology are being applied to the study of human brain tumours. These studies suggest that human brain tumours are organized as a hierarchy and are maintained by a small number of tumour cells that have stem cell properties. Most of the bulk population of human brain tumours comprise cells that have lost the ability to initiate and maintain tumour growth. Although the cell of origin for human brain tumours is uncertain, recent evidence points towards the brain's known proliferative zones. The identification of brain tumour stem cells has important implications for understanding brain tumour biology and these cells may be critical cellular targets for curative therapy.
    Philosophical Transactions of The Royal Society B Biological Sciences 02/2008; 363(1489):139-52. DOI:10.1098/rstb.2006.2017 · 7.06 Impact Factor
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    ABSTRACT: A 17-year-old male patient underwent surgery five times (four consecutive intracranial tumor removal surgeries and a final spinal tumor removal surgery). After the third surgery, this case was reported as a low-grade astroblastoma that is characterized by perivascular pseudorosettes consisting of elongated tumor cells arranged around the blood vessels. However, the fourth and fifth surgical specimens demonstrated very interesting histological changes in the astroblastoma. Through the course of relapses, the constituent cells of the astroblastic perivascular rosettes became smaller and rounder, and a multilayered cell arrangement was observed. The nucleus-to-cytoplasm ratio increased, and the compact intervascular cells ultimately lost glial fibrillary acidic protein (GFAP) expression. These undifferentiated cells showed high MIB-1 indices and an increased olig2 index. On the other hand, the cells in all the surgical specimens were positive for certain neuronal markers such as NSE, TUJ1, and nestin. Some astroblastomas may be more immature than the usual astrocytes; however, it is necessary to study more cases to confirm this.
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