Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain.
Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain.
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DOI：
10.1093/brain/awr094
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Steinberg GK
中科院分区：
文献类型：
--
作者：
Andres RH;Horie N;Slikker W;Keren-Gill H;Zhan K;Sun G;Manley NC;Pereira MP;Sheikh LA;McMillan EL;Schaar BT;Svendsen CN;Bliss TM;Steinberg GK
干细胞移植为治疗中风带来了新的希望，尽管移植细胞如何发挥作用仍存在重大问题。一种假设是移植的干细胞增强了脑缺血后激活的内源性修复机制。认识到存活回路的双侧重组与中风后的恢复有关，我们研究了移植的人类神经祖细胞增强这种结构可塑性的能力。我们的研究结果表明，第一个证据表明，人类神经祖细胞治疗可以显着增加在同侧和对侧皮质树突状可塑性，这与干细胞诱导的功能恢复相吻合。此外，干细胞移植大鼠表现出增加皮质，皮质纹状体，皮质丘脑和皮质脊髓轴突重新布线从contralesional侧;与transcallosa和皮质脊髓轴突发芽与功能恢复。此外，我们证明，轴突运输，这是至关重要的两个适当的轴突功能和轴突发芽，被中风抑制，这是由干细胞治疗挽救，从而确定另一种新的潜在机制的移植细胞的作用。最后，我们建立了体外共培养试验，其中这些干细胞模仿体内观察到的效果。通过免疫耗竭研究，我们确定了血管内皮生长因子，血小板反应蛋白1和2，和狭缝介导部分负责干细胞诱导的树突发芽，轴突可塑性和轴突运输在体外的影响。因此，我们推测人类神经前体细胞通过分泌增强脑修复和可塑性的因子来帮助中风后的恢复。
Stem cell transplantation promises new hope for the treatment of stroke although significant questions remain about how the grafted cells elicit their effects. One hypothesis is that transplanted stem cells enhance endogenous repair mechanisms activated after cerebral ischaemia. Recognizing that bilateral reorganization of surviving circuits is associated with recovery after stroke, we investigated the ability of transplanted human neural progenitor cells to enhance this structural plasticity. Our results show the first evidence that human neural progenitor cell treatment can significantly increase dendritic plasticity in both the ipsi- and contralesional cortex and this coincides with stem cell-induced functional recovery. Moreover, stem cell-grafted rats demonstrated increased corticocortical, corticostriatal, corticothalamic and corticospinal axonal rewiring from the contralesional side; with the transcallosal and corticospinal axonal sprouting correlating with functional recovery. Furthermore, we demonstrate that axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment, thus identifying another novel potential mechanism of action of transplanted cells. Finally, we established in vitro co-culture assays in which these stem cells mimicked the effects observed in vivo. Through immunodepletion studies, we identified vascular endothelial growth factor, thrombospondins 1 and 2, and slit as mediators partially responsible for stem cell-induced effects on dendritic sprouting, axonal plasticity and axonal transport in vitro. Thus, we postulate that human neural progenitor cells aid recovery after stroke through secretion of factors that enhance brain repair and plasticity.
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影响因子：
6.1
作者：
Benowitz LI;Carmichael ST
通讯作者：
Carmichael ST
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H
影响因子：
16.2
作者：
Conner, JM;Chiba, AA;Tuszynski, MH
通讯作者：
Tuszynski, MH
影响因子：
4.2
作者：
Guzman, Raphael;Bliss, Tonya;Steinberg, Gary
通讯作者：
Steinberg, Gary
影响因子：
11.2
作者：
Bang, OY;Lee, JS;Lee, G
通讯作者：
Lee, G