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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Hauptverfasser: Döppner, Thorsten Roland (VerfasserIn) , El Aanbouri, Mimount (VerfasserIn) , Dietz, Gunnar P. H. (VerfasserIn) , Weise, Jens (VerfasserIn) , Schwarting, Sönke (VerfasserIn) , Bähr, Mathias (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 8 June 2010
In: Neurobiology of disease
Year: 2010, Jahrgang: 40, Heft: 1, Pages: 265-276
ISSN:1095-953X
DOI:10.1016/j.nbd.2010.05.033
Online-Zugang: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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Verfasserangaben:Thorsten R. Doeppner, Mimount El Aanbouri, Gunnar P.H. Dietz, Jens Weise, Sönke Schwarting, Mathias Bähr

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520 |a 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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