Lentiviral vector-mediated genetic modification of human neural progenitor cells for ex vivo gene therapy

Capowski, Elizabeth E.; Schneider, Bernard L.; Ebert, Allison D.; Seehus, Corey R.; Szulc, Jolanta; Zufferey, Romain; Aebischer, Patrick; Svendsen, Clive N.

doi:10.1016/j.jneumeth.2007.02.022

Cited by 71 publications

(62 citation statements)

References 34 publications

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“…For lentiviral infections, the following viral constructs were used: SIN-PGK-GDNF-WPRE, SIN-PGK-IGF-1-WPRE and SIN-PGK-PreProNGF-BDNF-WPRE, constitutively expressing GDNF, IGF-1 and BDNF, respectively, under the control of phosphoglycerate kinase (PGK) promoter [25]. Viral titer used was 100 ng p24 capsid protein/10 6 cells.…”

Section: Generation Of Hnpc Transgenic Linesmentioning

confidence: 99%

BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons

Kitiyanant

Svendsen

et al. 2011

Neurochem Res

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Alzheimer's disease (AD) is characterized by the depositions of amyloid-β (Aβ) proteins, resulting in a reduction of choline acetyltransferase (ChAT) activity of AD brain in the early stages of the disease. Several growth factors, including brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF)-1 and glial cell-derived neurotrophic factor (GDNF) are known to protect neuronal cell death in several neurodegenerative both in vitro and in vivo models. In this study, septal neurons were prepared from septal nucleus of embryonic (day 16-17) rat brain and treated with monomeric, oligomeric or fibrillar Aβ(1-42) peptide. Oligomeric Aβ(1-42), (10 μM) was the most potent at sublethal dose. Septal neuron cultures treated with BDNF, IGF-1 or GDNF or co-cultured with genetically modified human neural progenitor cells (hNPCs) secreting these neurotrophic factors (but not allowing contact between the two cell types), were protected from oligomeric Aβ(1-42) peptide-induced cell death, and these trophic factors enhanced cholinergic functions by increasing ChAT expression level. These results indicate the potential of employing transplanted hNPCs for treatment of AD.

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Section: Generation Of Hnpc Transgenic Linesmentioning

confidence: 99%

BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons

Kitiyanant

Svendsen

et al. 2011

Neurochem Res

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“…3a-f; Johansson et al 1999;Kirschenbaum et al 1994;Kukekov et al 1999;Palmer et al 2001;Sanai et al 2004). This is tremendously exciting because it suggests that human SVZ cells could be surgically extracted, transduced to express genes that promote activation of cells and then transplanted back into patients (Capowski et al 2007). Human SVZ Fig.…”

Section: Human Svz Responses To Neural Injurymentioning

confidence: 99%

Activation of subventricular zone stem cells after neuronal injury

Kim

Szele

2007

Cell Tissue Res

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The mammalian subventricular zone (SVZ) has garnered a tremendous amount of attention as a potential source of replacement cells for neuronal injury. This zone is highly neurogenic, harbours stem cells and supports long-distance migration. The general pattern of activation includes increased proliferation, neurogenesis and emigration towards the injury. Intrinsic transcription factors and environmental signalling molecules are rapidly being discovered that may facilitate the induction of these cells to mount appropriate therapeutic responses. The extent of SVZ neurogenesis in humans is controversial. However, tantalizing new data suggest that humans are capable of generating increased numbers of neurons after a variety of diseases.

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“…Furthermore, FV particles can directly deliver genes into neural progenitor cells without the need for incorporation of foreign glycoproteins, whereas the human immunodeficiency virus-based gene delivery into central nervous system cells requires pseudotyping of virus particles. 42,43 In addition, the results of this study show that FV vectors can transfer genes with large regulatory DNA segments and mediate inducible gene expression.…”

Section: Foamy Viral Transduction Of Neural Progenitor Cells I Rothenmentioning

confidence: 70%

Transduction of human neural progenitor cells with foamy virus vectors for differentiation-dependent gene expression

et al. 2008

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Neural progenitor cells are potential vehicles for delivery of therapeutic agents into the brain. Differentiation-dependent promoters may be useful to target the therapeutic transgene expression to specific neural cell types. Here we explored the potential of vectors based on the foamy virus (FV) for genetic engineering of neural progenitor cells. We demonstrate that FV vectors can mediate stable long-term constitutive expression of the enhanced green fluorescent protein (EGFP) in neural progenitor cells. For differentiation-dependent gene expression, we constructed a FV vector with an internal expression cassette containing the human 2.2 kb promoter (Gfa2) of the astrocyte-specific glial fibrillary acidic protein (GFAP) and sequences encoding EGFP. We show FV-vector-mediated delivery of the Gfa2-egfp transgene into the human neural stem cell line HNSC.100 and differentiation-dependent expression in stably transduced cell populations. Differentiation of the FV-transduced HNSC.100 cells to astrocytes upregulated expression of both the Gfa2-egfp transgene and the native gfap gene, confirming differentiation-dependent activation of the transduced Gfa2 promoter. These results demonstrate that differentiation-dependent gene expression can be achieved by FV-vector-mediated gene transfer to neural progenitor cells. Our findings support the use of FV vectors for the genetic engineering of neural progenitor cells for therapeutic and research applications.

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Lentiviral vector-mediated genetic modification of human neural progenitor cells for ex vivo gene therapy

Cited by 71 publications

References 34 publications

BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons

BDNF-, IGF-1- and GDNF-Secreting Human Neural Progenitor Cells Rescue Amyloid β-Induced Toxicity in Cultured Rat Septal Neurons

Activation of subventricular zone stem cells after neuronal injury

Transduction of human neural progenitor cells with foamy virus vectors for differentiation-dependent gene expression

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