Analysis of adenovirus gene transfer into adult neural stem cells

Schmidt, Antje; Böckmann, Miriam; Stoll, Anja; Raček, Tomáš; Pützer, Brigitte M.

doi:10.1016/j.virusres.2005.05.010

Cited by 16 publications

(8 citation statements)

References 54 publications

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“…Neural precursor cells were isolated from adult C57BL/6 hippocampus (Charles River Laboratories, Wilmington, MA, http://www. criver.com) and expanded as previously described [15]. 293, H1299, Pan 02, and NIH 3T3 cell lines were obtained from American Type Culture Collection (Manassas, VA, http://www.atcc.org).…”

Section: Cell Culture and Peptidesmentioning

confidence: 99%

“…To identify peptide ligands that selectively bind NPC from adult mouse hippocampus, we used the phage display technology. Neural precursor cells in vitro were defined by their ability to self renew and to differentiate into glia and neurons [15]. Cultures of primary neurospheres established from the hippocampal area of adult C57BL/6 mice were incubated with a 7mer phage library that offers the possibility to identify small peptides.…”

Section: Introductionmentioning

confidence: 99%

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Selective Targeting of Adenoviral Vectors to Neural Precursor Cells in the Hippocampus of Adult Mice: New Prospects for In Situ Gene Therapy

et al. 2007

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The adult brain contains neural precursor cells (NPC) that are attracted to brain lesions, such as areas of neurodegeneration, ischemia, and cancer. This suggests that NPC engineered to promote lineage-specific differentiation or to express therapeutic genes might become a valuable tool for restorative cell therapy and for targeting therapeutic genes to diseased brain regions. Here we report the identification of NPC-specific ligands from phage display peptide libraries and show their potential to selectively direct adenovirusmediated gene transfer to NPC in adult mice. Identified peptides mediated specific virus binding and internalization to cultured neurospheres. Importantly, peptide-mediated adenoviral vector infection was restricted to precursor cells in the hippocampal dentate gyrus of pNestingreen fluorescent protein transgenic or C57BL/6 mice. Our approach represents a novel method for specific manipulation of NPC in the adult brain and may have major implications for the use of precursor cells as therapeutic delivery vehicles in the central nervous system.

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Section: Cell Culture and Peptidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective Targeting of Adenoviral Vectors to Neural Precursor Cells in the Hippocampus of Adult Mice: New Prospects for In Situ Gene Therapy

et al. 2007

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“…Recombined adenovirus vector (Ad), namely the recombined replicated-deficient adenovirus expression vector, can express levels of the target gene in nerve fibers, NSCs, and various other cell types (Falk, 2002;Mercier et al, 2004;Schmidt et al, 2005). The Ad does not insert its gene into the host cell genome, and therefore cannot disturb endogenous gene expression.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Parkinson disease with C17.2 neural stem cells overexpressing NURR1 with a recombined republic‐deficit adenovirus containing the NURR1 gene

Liu

Tang²,

Liu³

et al. 2007

Synapse

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To study the potential benefit of the NURR1 gene in Parkinson's disease (PD), we constructed a recombinant republic-deficit adenovirus containing the NURR1 gene (Ad-NURR1) and expressed it in transplanted neural stem cells (NSC). Ad-NURR1 was constructed, and NURR1 mRNA and protein expression were identified by in situ hybridization and western blot analysis, respectively. The identified NURR1 protein could directly or indirectly induce NSC differentiation into neurons. To identify a potential therapeutic use for the transfected NSCs, cells were transplanted into 6-hydroxydopamine lesioned rats. Histopathological and behavioral alterations were evaluated via immunohistochemistry and the ration test, respectively, in rats transplanted with NSCs with or without the Ad-NURR1 adenovirus. The Ad-NURR1 construct effectively expressed the NURR1 protein, which could directly or indirectly induce NSC differentiation into neurons. Both histopathological and behavioral alterations were seen in rats treated with NSCs with or without the Ad-NURR1 construct, although in the case of the latter, the benefits were more robust. These results suggest a potential therapeutic benefit for Ad-NURR1-expressing cells in the treatment of PD. The Ad-NURR1 modification induced NSC differentiation and therefore represents a potential therapy for PD.

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“…Procedures utilizing Ad-EGFP under the control of the mCMV promoter have been described previously (22,23). Briefly, the virus was packaged in 293 cells (Benyuan Zhengyang Gene Technology Co., Ltd., Beijing, China), amplified using the AdMax™ virus purification kit (Benyuan Zhengyang Gene Technology Co., Ltd.) according to the manufacturer's protocol, and titrated as previously described (24). …”

Section: Methodsmentioning

confidence: 99%

Hes1 negatively regulates neurogenesis in the adult mouse dentate gyrus following traumatic brain injury

Yao

Zhang

et al. 2018

Exp Ther Med

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Traumatic brain injury (TBI) results in the activation of neurogenesis, but it also triggers multiple cell signaling pathways that may lead to either cell damage or cell survival. In general, the repair processes following TBI are characterized by a failure to replenish the neuronal population entirely. To date, the factors that determine whether neurogenesis will be sufficient for the replacement of lost neurons following brain injury are not fully understood. Decreased activation of Hes1, a transcriptional repressor, is observed as neural differentiation proceeds, and this gene continues to play a role in the quiescence of stem cells into adulthood. Since Hes1 is negatively correlated with neurogenesis in adult rodents, the present study investigated whether this gene inhibits TBI-induced neurogenesis by use of adenovirus-mediated gene transfer to upregulate Hes1 expression in the dentate gyrus (DG) in a mouse model of TBI. Western blot analysis and immunofluorescent staining revealed increased Hes1 protein expression in the subgranular zone (SGZ) of the DG following adenovirus-Hes1 (Ad-Hes1) transfection and a decreased number of bromodeoxyuridine-positive and doublecortin-positive cells in the SGZ in the transfection group following TBI. These data indicated a negative association between the expression of Hes1 and adult neurogenesis following the induction of TBI. Furthermore, the present findings demonstrate the value of downregulating Hes1 expression following TBI to promote the initiation of endogenous neurogenesis, which may be of therapeutic value for patients with brain injuries.

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Analysis of adenovirus gene transfer into adult neural stem cells

Cited by 16 publications

References 54 publications

Selective Targeting of Adenoviral Vectors to Neural Precursor Cells in the Hippocampus of Adult Mice: New Prospects for In Situ Gene Therapy

Selective Targeting of Adenoviral Vectors to Neural Precursor Cells in the Hippocampus of Adult Mice: New Prospects for In Situ Gene Therapy

Treatment of Parkinson disease with C17.2 neural stem cells overexpressing NURR1 with a recombined republic‐deficit adenovirus containing the NURR1 gene

Hes1 negatively regulates neurogenesis in the adult mouse dentate gyrus following traumatic brain injury

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