Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain
The use of ex vivo gene therapy in the central nervous system has so far suffered from transgene downregulation. Condensation of the transgenic sequences has been proposed to be a mechanism involved in this silencing. In this study we inhibited either histone deacetylation or DNA methylation in neur...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2005-02-01
|
| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000005783983188 |
| _version_ | 1811222323669237760 |
|---|---|
| author | Nina Rosenqvist Johan Jakobsson Cecilia Lundberg |
| author_facet | Nina Rosenqvist Johan Jakobsson Cecilia Lundberg |
| author_sort | Nina Rosenqvist |
| collection | DOAJ |
| description | The use of ex vivo gene therapy in the central nervous system has so far suffered from transgene downregulation. Condensation of the transgenic sequences has been proposed to be a mechanism involved in this silencing. In this study we inhibited either histone deacetylation or DNA methylation in neural progenitor cell lines, transduced with a lentiviral vector carrying green fluorescent protein (GFP), prior to grafting them into the rat striatum. The expression of GFP was significantly higher in grafts pretreated with either of the inhibitors. After 1 week in vivo we detected an 11-fold increase in the number of GFP-expressing cells due to the inhibition of DNA methylation in vitro with azadeoxycytidine and a ninefold increase when inhibiting histone deacetylation with trichostatin A. This suggests that a pretreatment paradigm could be used to increase efficacy of ex vivo delivery of a therapeutic protein locally in the brain. |
| first_indexed | 2024-04-12T08:13:49Z |
| format | Article |
| id | doaj.art-d589f943154d422d90e14576b31b6c51 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-04-12T08:13:49Z |
| publishDate | 2005-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-d589f943154d422d90e14576b31b6c512022-12-22T03:40:53ZengSAGE PublishingCell Transplantation0963-68971555-38922005-02-011410.3727/000000005783983188Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat BrainNina Rosenqvist0Johan Jakobsson1Cecilia Lundberg2Wallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, Lund, SwedenWallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, Lund, SwedenWallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, Lund, SwedenThe use of ex vivo gene therapy in the central nervous system has so far suffered from transgene downregulation. Condensation of the transgenic sequences has been proposed to be a mechanism involved in this silencing. In this study we inhibited either histone deacetylation or DNA methylation in neural progenitor cell lines, transduced with a lentiviral vector carrying green fluorescent protein (GFP), prior to grafting them into the rat striatum. The expression of GFP was significantly higher in grafts pretreated with either of the inhibitors. After 1 week in vivo we detected an 11-fold increase in the number of GFP-expressing cells due to the inhibition of DNA methylation in vitro with azadeoxycytidine and a ninefold increase when inhibiting histone deacetylation with trichostatin A. This suggests that a pretreatment paradigm could be used to increase efficacy of ex vivo delivery of a therapeutic protein locally in the brain.https://doi.org/10.3727/000000005783983188 |
| spellingShingle | Nina Rosenqvist Johan Jakobsson Cecilia Lundberg Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain Cell Transplantation |
| title | Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain |
| title_full | Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain |
| title_fullStr | Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain |
| title_full_unstemmed | Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain |
| title_short | Inhibition of Chromatin Condensation Prevents Transgene Silencing in a Neural Progenitor Cell Line Transplanted to the Rat Brain |
| title_sort | inhibition of chromatin condensation prevents transgene silencing in a neural progenitor cell line transplanted to the rat brain |
| url | https://doi.org/10.3727/000000005783983188 |
| work_keys_str_mv | AT ninarosenqvist inhibitionofchromatincondensationpreventstransgenesilencinginaneuralprogenitorcelllinetransplantedtotheratbrain AT johanjakobsson inhibitionofchromatincondensationpreventstransgenesilencinginaneuralprogenitorcelllinetransplantedtotheratbrain AT cecilialundberg inhibitionofchromatincondensationpreventstransgenesilencinginaneuralprogenitorcelllinetransplantedtotheratbrain |