Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.
Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.
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DOI：
10.1371/journal.pone.0050444
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Thuret S
中科院分区：
文献类型：
--
作者：
Hassani Z;O'Reilly J;Pearse Y;Stroemer P;Tang E;Sinden J;Price J;Thuret S
干细胞移植是目前治疗慢性缺血性脑卒中最有前途的方法之一。人条件永生化神经干细胞系CTX 0E03在啮齿动物中风模型中具有可证实的疗效，目前正在进行临床试验。尽管如此，它促进大脑修复的机制还没有完全确定。本研究调查了CTX0E03移植到缺血性卒中大鼠脑中后发生的细胞事件。 我们专注于宿主脑对细胞移植的内源性增殖活性，并使用年轻神经元（doublecortin，Dcx）和小胶质细胞（CD11b）的标记物确定增殖细胞的身份。为了确定移植后发生事件的时间顺序，我们分析了移植后一周和四周的移植脑。 我们观察到，与载体治疗的缺血性脑相比，接受CTX 0E03移植物的缺血性脑的纹状体中的内源性增殖显著更大。发现这些增殖细胞中的显著比例是Dcx+纹状体成神经细胞。此外，我们描述了CTX0E03植入后增强的免疫应答，如增殖的CD11b+小胶质细胞的显著增加所示。 我们的研究表明，在正常情况下，很少有Dcx+神经母细胞是增殖的，并且这种增殖性神经母细胞的群体在对中风的反应中增加。我们进一步表明，中风后移植CTX 0E03可维持这种增殖活性。有趣的是，在CTX 0E03移植后神经元增殖活性的保留之前并伴随着高增殖率的小胶质细胞。我们的研究表明，小胶质细胞可能部分介导缺血性卒中条件下CTX 0E03移植对神经元增殖的影响。
Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised. This study investigated the cellular events occurring after CTX0E03 transplantation in the brains of rats that underwent ischemic stroke. We focused on the endogenous proliferative activity of the host brain in response to cell transplantation and determined the identity of the proliferating cells using markers for young neurons (doublecortin, Dcx) and microglia (CD11b). So as to determine the chronology of events occurring post-transplantation, we analysed the engrafted brains one week and four weeks post-transplantation. We observed a significantly greater endogenous proliferation in the striatum of ischemic brains receiving a CTX0E03 graft compared to vehicle-treated ischemic brains. A significant proportion of these proliferative cells were found to be Dcx+ striatal neuroblasts. Further, we describe an enhanced immune response after CTX0E03 engraftment, as shown by a significant increase of proliferating CD11b+ microglial cells. Our study demonstrates that few Dcx+ neuroblasts are proliferative in normal conditions, and that this population of proliferative neuroblasts is increased in response to stroke. We further show that CTX0E03 transplantation after stroke leads to the maintenance of this proliferative activity. Interestingly, the preservation of neuronal proliferative activity upon CTX0E03 transplantation is preceded and accompanied by a high rate of proliferating microglia. Our study suggests that microglia might mediate in part the effect of CTX0E03 transplantation on neuronal proliferation in ischemic stroke conditions.
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影响因子：
3.7
作者：
Tajiri N;Acosta S;Glover LE;Bickford PC;Jacotte Simancas A;Yasuhara T;Date I;Solomita MA;Antonucci I;Stuppia L;Kaneko Y;Borlongan CV
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1.9
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1.6
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Price, Jack
影响因子：
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