A comparative study of the structural organization of spheres derived from the adult human subventricular zone and glioblastoma biopsies |
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Authors: | Vik-Mo Einar Osland Sandberg Cecilie Joel Mrinal Stangeland Biljana Watanabe Yasuhiro Mackay-Sim Alan Moe Morten Carstens Murrell Wayne Langmoen Iver Arne |
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Institution: | aVilhelm Magnus Laboratory for Neurosurgical Research, Institute for Surgical Research, Oslo University Hospital, Oslo, Norway;bDepartment of Neurosurgery, Oslo University Hospital, Oslo, Norway;cDepartment of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway;dDivision of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan;eNational Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, QLD 4111, Australia;fCenter for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway |
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Abstract: | Sphere forming assays have been useful to enrich for stem like cells in a range of tumors. The robustness of this system contrasts the difficulties in defining a stem cell population based on cell surface markers. We have undertaken a study to describe the cellular and organizational composition of tumorspheres, directly comparing these to neurospheres derived from the adult human subventricular zone (SVZ). Primary cell cultures from brain tumors were found to contain variable fractions of cells positive for tumor stem cell markers (CD133 (2–93%)/SSEA1 (3–15%)/CXCR4 (1–72%)). All cultures produced tumors upon xenografting. Tumorspheres contained a heterogeneous population of cells, but were structurally organized with stem cell markers present at the core of spheres, with markers of more mature glial progenitors and astrocytes at more peripheral location. Ultrastructural studies showed that tumorspheres contained a higher fraction of electron dense cells in the core than the periphery (36% and 19%, respectively). Neurospheres also contained a heterogeneous cell population, but did not have an organization similar to tumorspheres. Although tumorspheres clearly display irregular and neoplastic cells, they establish an organized structure with an outward gradient of differentiation. We suggest that this organization is central in maintaining the tumor stem cell pool. |
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Keywords: | Abbreviations: BSA bovine serum albumin FCS fetal calf serum GFAP glial fibrillary acidic protein IF intermediate filaments PBS phosphate buffered saline SSEA1 stage specific embryonal antigen 1 CD15 Lewis x SVZ subventricular zone |
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