Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: Growth of processes into the organ of corti
Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: Growth of processes into the organ of corti
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DOI：
10.1002/neu.20310
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发表时间：
2006-11-01
期刊：
影响因子：
--
通讯作者：
Edge, Albert S. B.
中科院分区：
文献类型：
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作者：
Corrales, C. Eduardo;Pan, Luying;Edge, Albert S. B.
哺乳动物的听力损失是不可逆的，因为耳蜗神经元和毛细胞不能再生。为了确定我们是否可以取代神经元损失的主要神经元变性，我们注射EYFP表达胚胎干细胞衍生的小鼠神经祖细胞到耳蜗神经干免疫抑制动物1周后，破坏耳蜗神经（螺旋神经节）细胞，而留下毛细胞完整的哇巴因应用于圆窗在沙鼠耳蜗的基础。在移植后3天，观察到表达内源性EYFP的小移植物，并且可以免疫标记神经元特异性标记物。移植后12天，移植物具有从神经核心向去神经支配的Corti器官延伸的神经元。到64-98天，移植物发出了丰富的突起，占据了以前由耳蜗神经占据的空间的很大一部分。神经突成束状生长，穿过罗森塔尔管（螺旋神经节细胞的前身），进入骨螺旋板，最终进入Corti器官，在那里它们接触毛细胞。神经元计数显示在感觉上皮附近的神经元突起显著增加，与去神经支配而没有随后的干细胞移植的动物相比。这些神经元的再生表明，从干细胞分化的神经元具有在神经元变性的动物模型中生长至特定靶点的能力。(c)2006 Wiley Periodicals，Inc.
Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell-derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals I week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen that expressed endogenous EYFP and could be immunolabeled for neuron-specific markers. Twelve days after transplantation, the grafts had neurons that extended processes from the nerve core toward the denervated organ of Corti. By 64-98 days, the grafts had sent out abundant processes that occupied a significant portion of the space formerly occupied by the cochlear nerve. The neurites grew in fasciculating bundles projecting through Rosenthal's canal, the former site of spiral ganglion cells, into the osseous spiral lamina and ultimately into the organ of Corti, where they contacted hair cells. Neuronal counts showed a significant increase in neuronal processes near the sensory epithelium, compared to animals that were denervated without subsequent stem cell transplantation. The regeneration of these neurons shows that neurons differentiated from stem cells have the capacity to grow to a specific target in an animal model of neuronal degeneration. (c) 2006 Wiley Periodicals, Inc.