Transplantation of TAT-Bcl-x_L-transduced neural precursor cells: Long-term neuroprotection after stroke

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• 作者：Thorsten R. Doeppner ; Mimount El Aanbouri ; Gunnar P.H. Dietz ; Jens Weise ; Sö ; nke Schwarting ; Mathias Bä ; hr
• 关键词：Cerebral ischemia ; Neural precursor cells ; Neurogenesis ; Ttroke ; TAT-Bcl-x_L
• 刊名：Neurobiology of Disease
• 出版年：2010
• 出版时间：October 2010
• 年：2010
• 卷：40
• 期：1
• 页码：265-276
• 全文大小：1458 K

文摘

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-x_L and analyzed NPC survival, differentiation, and post-stroke functional deficits after experimental ischemia in mice. Survival of TAT-Bcl-x_L-transduced NPC, which were injected at day 7 post-stroke into the ischemic striatum, was significantly increased at 4 weeks after stroke. Increased survival of NPC was associated with reduced infarct injury and decreased post-stroke functional deficits. Animals grafted with TAT-Bcl-x_L-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-x_L results in enhanced resistance of transplanted NPC followed by long-term neuroprotection and ameliorated functional deficits after transient focal cerebral ischemia in mice.