Neurosphere

About: Neurosphere is a research topic. Over the lifetime, 5145 publications have been published within this topic receiving 321088 citations.

The extracellular matrix compartment of neural stem and glial progenitor cells.

Abstract: Neuroepithelial and radial GLIA stem cells generate the majority of the cellular constituents of the central nervous system. Following precisely timed phases of neurogenesis and gliogenesis the stem cells recede, with the exception of adult neural stem cells that persist in two generally accepted canonical neurogenic regions, the subventricular zone of the lateral ventricle and the subgranular zone in the dentate gyrus of the hippocampus. It is believed that adult stem cells reside in privileged stem cell niche environments that provide favorable conditions for self-renewal and maintenance of this cellular compartment. Factors such as morphogens, cytokines, and growth factors influence the developmental pathway of neural stem/progenitor cells. By comparison, less is known about the regulatory roles of glycoproteins and proteoglycans of the extracellular matrix (ECM) and their receptors, although they represent important constituents of the micromolecular environment of the niche. Here, we summarize studies that indicate pivotal roles of the ECM micromilieu for the biology and instrumental use of glial stem and progenitor cells of the CNS. Advancing our understanding of structure-function relationships, signaling motifs and complementary receptors and their signal transduction pathways will be of central importance for the application of these cell types in regenerative medicine.

TLR2 activation inhibits embryonic neural progenitor cell proliferation

Abstract: Toll-like receptors (TLRs) play essential roles in innate immunity, and increasing evidence indicates that these receptors are expressed in neurons, astrocytes, and microglia in the brain, where they mediate responses to infection, stress, and injury. To address the possibility that TLR2 heterodimer activation could affect progenitor cells in the developing brain, we analyzed the expression of TLR2 throughout mouse cortical development, and assessed the role of TLR2 heterodimer activation in neuronal progenitor cell (NPC) proliferation. TLR2 mRNA and protein was expressed in the cortex in embryonic and early postnatal stages of development, and in cultured cortical NPC. While NPC from TLR2-deficient and wild type embryos had the same proliferative capacity, TLR2 activation by the synthetic bacterial lipopeptides Pam(3)CSK(4) and FSL1, or low molecular weight hyaluronan, an endogenous ligand for TLR2, inhibited neurosphere formation in vitro. Intracerebral in utero administration of TLR2 ligands resulted in ventricular dysgenesis characterized by increased ventricle size, reduced proliferative area around the ventricles, increased cell density, an increase in phospho-histone 3 cells, and a decrease in BrdU(+) cells in the sub-ventricular zone. Our findings indicate that loss of TLR2 does not result in defects in cerebral development. However, TLR2 is expressed and functional in the developing telencephalon from early embryonic stages and infectious agent-related activation of TLR2 inhibits NPC proliferation. TLR2-mediated inhibition of NPC proliferation may therefore be a mechanism by which infection, ischemia, and inflammation adversely affect brain development.

Brain tumor stem cells.

Abstract: Primary malignant brain cancer, one of the most deadly diseases, has a high rate of recurrence after treatment. Studies in the past several years have led to the hypothesis that the root of the recurrence may be brain tumor stem cells (BTSCs), stem-like subpopulation of cells that are responsible for propagating the tumor. Current treatments combining surgery and chemoradiotherapy could not eliminate BTSCs because these cells are highly infiltrative and possess several properties that can reduce the damages caused by radiation or anti-cancer drugs. BTSCs are similar to NSCs in molecular marker expression and multi-lineage differentiation potential. Genetic analyses of Drosophila CNS neoplasia, mouse glioma models, and human glioma tissues have revealed a link between increased NSC self-renewal and brain tumorigenesis. Furthermore, data from various rodent models of malignant brain tumors have provided compelling evidence that multipotent NSCs and lineage-restricted neural progenitor cells (NPCs) could be the cell origin of brain tumors. Thus, the first event of brain tumorigenesis might be the occurrence of oncogenic mutations in the stem cell self-renewal pathway in an NSC or NPC. These mutations convert the NSC or NPC to a BTSC, which then initiates and sustains the growth of the tumor. The self-renewal of BTSCs is controlled by several evolutionarily conserved signaling pathways and requires an intact vascular niche. Targeting these pathways and the vascular niche could be a principle in novel brain tumor therapies aimed to eliminate BTSCs.

Growth factor-induced proliferation of neural precursor cells in vivo

Abstract: A method is described for inducing in vivo proliferation of precursor cells located in mammalian neural tissue by administering to the mammal a fibroblast growth factor and at least one additional growth factor selected from the group consisting of epidermal growth factor, transforming growth factor alpha, and amphiregulin. The method can be used to replace damaged or missing neurons and/or glia. Another method is described for transplanting multipotent neural stem cell progeny into a mammal. The method comprises the steps of administering growth factors to a mammal to induce in vivo proliferation of neural precursor cells, removing the precursor cell progeny from the mammal, culturing the removed cells in vitro in the presence of one or more growth factors that induces multipotent neural stem cell proliferation, and implanting the multipotent neural stem cell progeny into the mammal.