Transplantation of TAT-Bcl-xL-transduced neural precursor cells: long-term neuroprotection after stroke
Neural precursor cells (NPC) are an interesting tool in experimental stroke research, but their therapeutic potential is limited due to poor long-term survival. We therefore in vitro transduced subventricular zone-(SVZ)-derived NPC with the anti-apoptotic fusion protein TAT-Bcl-xL and analyzed NPC s...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
8 June 2010
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| In: |
Neurobiology of disease
Year: 2010, Volume: 40, Issue: 1, Pages: 265-276 |
| ISSN: | 1095-953X |
| DOI: | 10.1016/j.nbd.2010.05.033 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.nbd.2010.05.033 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0969996110001956 
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| Author Notes: | Thorsten R. Doeppner, Mimount El Aanbouri, Gunnar P.H. Dietz, Jens Weise, Sönke Schwarting, Mathias Bähr |
| Summary: | Neural precursor cells (NPC) are an interesting tool in experimental stroke research, but their therapeutic potential is limited due to poor long-term survival. We therefore in vitro transduced subventricular zone-(SVZ)-derived NPC with the anti-apoptotic fusion protein TAT-Bcl-xL and analyzed NPC survival, differentiation, and post-stroke functional deficits after experimental ischemia in mice. Survival of TAT-Bcl-xL-transduced NPC, which were injected at day 7 post-stroke into the ischemic striatum, was significantly increased at 4weeks after stroke. Increased survival of NPC was associated with reduced infarct injury and decreased post-stroke functional deficits. Animals grafted with TAT-Bcl-xL-transduced NPC showed an increased number of immature cells expressing the neuronal marker doublecortin. Since mature neuronal differentiation of NPC was not observed, reduced post-stroke injury cannot be attributed to enhanced neuronal regeneration, but rather to indirect by-stander effects of grafted NPC. In line with this, NPC-mediated neuroprotection of cortical neurons in vitro was associated with increased secretion of growth factors. Thus, in vitro transduction of cultivated NPC with TAT-Bcl-xL results in enhanced resistance of transplanted NPC followed by long-term neuroprotection and ameliorated functional deficits after transient focal cerebral ischemia in mice. |
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| Item Description: | Im Titel ist der Buchstabe "L" bei "xL" tiefgestellt Gesehen am 13.02.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1095-953X |
| DOI: | 10.1016/j.nbd.2010.05.033 |