Huttner Hagen B, Janich Peggy, Köhrmann Martin, Jászai József, Siebzehnrubl Florian, Blümcke Ingmar, Suttorp Meinolf, Gahr Manfred, Kuhnt Daniela, Nimsky Christopher, Krex Dietmar, Schackert Gabriele, Löwenbrück Kai, Reichmann Heinz, Jüttler Eric, Hacke Werner, Schellinger Peter D, Schwab Stefan, Wilsch-Bräuninger Michaela, Marzesco Anne-Marie, Corbeil Denis
Tissue Engineering Laboratories, Biotechnology Center (BIOTEC), Technische Universität Dresden, Tatzberg 47-51, 01307 Dresden, Germany.
Stem Cells. 2008 Mar;26(3):698-705. doi: 10.1634/stemcells.2007-0639. Epub 2007 Dec 20.
Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associated with whole cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry prominin-1/CD133, a neural stem cell marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation and detergent solubility analyses showed that these membrane particles were similar in physical properties and microdomain organization to small membrane vesicles previously shown to be released from neural stem cells in the mouse embryo. The levels of membrane particle-associated prominin-1/CD133 declined during childhood and remained constant thereafter, with a remarkably narrow range in healthy adults. Glioblastoma patients showed elevated levels of membrane particle-associated prominin-1/CD133, which decreased dramatically in the final stage of the disease. Hence, analysis of CSF for membrane particles carrying the somatic stem cell marker prominin-1/CD133 offers a novel approach for studying human central nervous system disease.
脑脊液(CSF)通常用于诊断和监测神经疾病。迄今为止用于诊断目的的脑脊液蛋白质(与全细胞相关的蛋白质除外)都是可溶的。在此,我们表明人类脑脊液含有携带prominin-1/CD133的特定膜颗粒,prominin-1/CD133是一种与脑肿瘤尤其是胶质母细胞瘤相关的神经干细胞标志物。差速离心和平衡离心以及去污剂溶解性分析表明,这些膜颗粒在物理性质和微结构组织方面与先前显示从小鼠胚胎神经干细胞释放的小膜泡相似。与膜颗粒相关的prominin-1/CD133水平在儿童期下降,此后保持恒定,在健康成年人中范围非常窄。胶质母细胞瘤患者显示与膜颗粒相关的prominin-1/CD133水平升高,在疾病末期急剧下降。因此,分析脑脊液中携带体细胞干细胞标志物prominin-1/CD133的膜颗粒为研究人类中枢神经系统疾病提供了一种新方法。