Huhn Stephen L, Yung Yun, Cheshier Samuel, Harsh Griffith, Ailles Laurie, Weissman Irving, Vogel Hannes, Tse Victor
Department of Neurosurgery, Stanford University, California 94305-5327, USA.
J Neurosurg. 2005 Nov;103(5 Suppl):446-50. doi: 10.3171/ped.2005.103.5.0446.
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.
本研究的目的是阐明小儿成星形细胞瘤内一个重要亚群细胞的研究结果,这些细胞具有已知人类神经干细胞所具有的特定细胞表面表型。
利用荧光激活细胞分选技术,从一名11岁女孩大脑中切除的几乎不进行有丝分裂的成星形细胞瘤中分离出具有人类神经干细胞特征性细胞表面标志物谱的细胞。异常高比例(24%)的细胞CD133阳性,CD24、CD34和CD45阴性(CD133(+)CD24(-)CD34(-)CD45(-)细胞),这是与神经干细胞相关的表型抗原模式;很少有CD133阳性细胞不同时为CD24、CD34和CD45阴性。一些细胞(12%)CD34阳性,表明肿瘤内存在造血干细胞。将细胞接种到干细胞培养基中时,它们形成了类似于神经球的细胞球,共表达β-微管蛋白和胶质纤维酸性蛋白(GFAP),但不表达少突胶质细胞标志物O4。通过掺入溴脱氧尿苷证明细胞增殖。细胞在传代四到六次后失去了体外自我更新的能力,尽管它们继续共表达β-微管蛋白和GFAP。当置于分化培养基中时,这些细胞不会分化为神经元或星形胶质细胞。
尽管该成星形细胞瘤含有高比例的表型神经干细胞样细胞,但这些细胞的增殖能力和多能性有限。它们在成星形细胞瘤形成和生长中的作用尚不清楚。