title: Adult neural stem cells from the subventricular zone: a review of the neurosphere assay.
abstract: The possibility of obtaining large numbers of cells with potential to become functional neurons implies a great advance in regenerative medicine. A source of cells for therapy is the subventricular zone (SVZ) where adult neural stem cells (NSCs) retain the ability to proliferate, self-renew, and differentiate into several mature cell types. The neurosphere assay, a method to isolate, maintain, and expand these cells has been extensively utilized by research groups to analyze the biological properties of aNSCs and to graft into injured brains from animal models. In this review we briefly describe the neurosphere assay and its limitations, the methods to optimize culture conditions, the identity and the morphology of aNSC-derived neurospheres (including new ultrastructural data). The controversy regarding the identity and "stemness" of cells within the neurosphere is revised. The fine morphology of neurospheres, described thoroughly, allows for phenotypical characterization of cells in the neurospheres and may reveal slight changes that indirectly inform about cell integrity, cell damage, or oncogenic transformation. Along this review we largely highlight the critical points that researchers have to keep in mind before extrapolating results or translating experimental transplantation of neurosphere-derived cells to the clinical setting.
authors.affiliation: Laboratory of Comparative Neurobiology, Instituto Cavanilles de Biodiversidad y Biología Evolutiva, University of Valencia, C/Catedratico Jose Beltran no 2, Paterna, Valencia, CIBERNED, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Gil-Perotín
authors.forename: María
authors.initials: M
authors.lastname: Duran-Moreno
authors.forename: Arantxa
authors.initials: A
authors.lastname: Cebrián-Silla
authors.forename: Mónica
authors.initials: M
authors.lastname: Ramírez
authors.forename: Paula
authors.initials: P
authors.lastname: García-Belda
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Verdugo
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001681:Biological Assay / Q000379:methods*; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis; D010641:Phenotype; D044968:Regenerative Medicine / Q000379:methods; D018874:Spheroids, Cellular; D033581:Stem Cell Transplantation
chemical_list: D015415:Biomarkers
keywords: SVZ; adult neurogenesis; neurosphere; olfaction