Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury.
Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury.
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DOI：
10.3389/fncel.2013.00128
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发表时间：
2013
影响因子：
5.3
通讯作者：
Suzuki M
中科院分区：
文献类型：
--
作者：
Shinoyama M;Ideguchi M;Kida H;Kajiwara K;Kagawa Y;Maeda Y;Nomura S;Suzuki M
新生儿缺氧缺血性脑病（HIE）可导致脑性瘫痪（CP）、精神发育迟滞和癫痫，这些症状会持续终生。然而，目前很少有用于缺血组织的恢复性治疗。细胞替代疗法提供了挽救由HI引起的脑损伤和恢复运动功能的潜力。在本研究中，我们评估了胚胎干细胞衍生的神经前体细胞（ES-NPCs）成为皮层深层神经元，恢复神经网络，并修复脑损伤的HIE小鼠模型的能力。通过基质细胞共培养将稳定表达报告基因GFP的ES细胞诱导至神经前体状态。在诱导HIE后40小时，将动物移植有靶向缺血脑中运动皮质深层的ES-NPC。移植后3周评价运动功能。用免疫组织化学和GFP神经解剖示踪分析神经元分化和轴突发芽。ES-NPCs可分化为锥体细胞形态的皮质神经元，并表达深层特异性标志物Ctip 2。移植物表现出良好的存活和适当的神经支配模式，通过轴突发芽从移植细胞在缺血脑。与假移植组相比，移植的HIE小鼠的运动功能也显著改善。这些发现表明，皮质区域特异性植入预处理的皮质前体细胞可以支持HIE模型中的运动功能恢复。目前尚不清楚这是移植细胞的直接作用还是由于这些细胞产生的神经营养因子。这些结果表明，皮质区域特异性NPC植入是一种有前途的脑修复治疗方法。
Hypoxic-ischemic encephalopathy (HIE) at birth could cause cerebral palsy (CP), mental retardation, and epilepsy, which last throughout the individual's lifetime. However, few restorative treatments for ischemic tissue are currently available. Cell replacement therapy offers the potential to rescue brain damage caused by HI and to restore motor function. In the present study, we evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model. ES cells stably expressing the reporter gene GFP are induced to a neural precursor state by stromal cell co-culture. Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical tracing with GFP were used to analyze neuronal differentiation and axonal sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal morphology and expressed the deep layer-specific marker, Ctip2. The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model. It is not clear whether this is a direct effect of the engrafted cells or due to neurotrophic factors produced by these cells. These results suggest that cortical region-specific NPC engraftment is a promising therapeutic approach for brain repair.
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影响因子：
3.7
作者：
Kida H;Nomura S;Shinoyama M;Ideguchi M;Owada Y;Suzuki M
通讯作者：
Suzuki M
影响因子：
8.3
作者：
Borlongan, CV;Hadman, M;Sanberg, PR
通讯作者：
Sanberg, PR
影响因子：
25
作者：
Gaillard, Afsaneh;Prestoz, Laetitia;Jaber, Mohamed
通讯作者：
Jaber, Mohamed
影响因子：
168.9
作者：
Gluckman, PD;Wyatt, JS;Gunn, AJ
通讯作者：
Gunn, AJ
影响因子：
4.2
作者：
Ideguchi, Makoto;Shinoyama, Mizuya;Takahashi, Jun
通讯作者：
Takahashi, Jun