Vroemen, Maurice and Weidner, Norbert and Blesch, A. (2005) Loss of gene expression in lentivirus- and retrovirus-transduced neural progenitor cells is correlated to migration and differentiation in the adult spinal cord. EXPERIMENTAL NEUROLOGY, 195 (1). pp. 127-139. ISSN 0014-4886, 1090-2430
Full text not available from this repository. (Request a copy)Abstract
Gene transfer into multipotent neural progenitor cells (NPC) and stem cells may provide for a cell replacement therapy and allow the delivery of therapeutic proteins into the degenerating or injured nervous system. Previously, murine leukemia virus-based retroviral vectors expressing GFP from an internal EF-I alpha promoter and lentiviral vectors expressing GFP from a hybrid CMV/beta-actin promoter have been described to be resistant to stem cell specific gene silencing. Therefore, we investigated whether these viral vectors allow stable in vivo gene expression in genetically modified NPC isolated from the adult rat spinal cord. In vitro, NPC genetically modified to express GFP using the described retroviral vector showed strong GFP expression in undifferentiated NPC. However, in vitro differentiation resulted in the loss of GFP expression in 50% of cells. Grafting of BrdU-prelabeled NPC to the spinal cord resulted in a loss of GFP expression in 70% and 95% of surviving NPC at 7 and 28 days post-grafting, respectively. The loss in gene expression was paralleled by the differentiation of NPC into a glial phenotype. Transgene downregulation although less profound was also observed in cells modified with lentiviral vectors, whereas in vivo lentiviral gene transfer resulted in stable transgene expression for up to 16 months. Thus, in vivo gene expression in genetically engineered neural progenitor cells is temporally limited and mostly restricted to undifferentiated NPC using the viral vectors tested. (c) 2005 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EMBRYONIC STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; PARKINSONS-DISEASE; AXONAL GROWTH; RAT MODEL; VECTOR; NEURONS; GRAFTS; DELIVERY; neural progenitor cells; retrovirus; lentivirus; gene therapy; transplantation; transgene silencing |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Apr 2021 12:26 |
| Last Modified: | 27 Apr 2021 12:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35684 |
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