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The effect of neuronal stem cell for ischemia reperfusion injury of the cochlea

神经干细胞对耳蜗缺血再灌注损伤的作用

基本信息

批准号：
16591712
负责人：
HAKUBA Nobuhiro
金额：
$ 2.37万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591712/
关键词：
neuronal stem cells (NSCs)cochlear ischemia inner hair cell (IHC)cell therapy regeneration gerbil 感音性難聴再生治療 Auditory Brainstem response 内耳虚血障害細胞移植微細ガラス管

项目摘要

Neural stem cells (NSCs) are multipotent progenitor cells that have self-renewal activity. The use of NSCs has recently provided a novel strategy for production of cells of the central nerve system (CNS), including neurons, astrocytes, and oligodendrocytes. In this study, we assessed the utility of NSCs for the amelioration of ischemia-reperfusion injury of the gerbil cochlea. NSCs were injected into one inner ear through the round window, one day after bilateral ischemic insult ; the other ear served as the untreated control. Immunostaining for nestin showed that the distribution of NSCs was concentrated in the organ of Corti at the basal cochlear turn. To evaluate the engraftment of NSCs, neurosphere cells were transduced with adenoviral vectors expressing β-galactosidase before transplantation, and their presence in the cochleae was demonstrated using X-gal staining 3 days after transfer. The hearing ability on the transplanted side was compared with that on the control side by sequential recordings of the auditory brainstem response (ABR). On the fourth day of ischemia, the injury-induced shift in the ABR threshold was remarkably suppressed on the NSC-transplanted side as compared to the control side. These results suggest that transplantation of NSCs is therapeutically useful for prevention of the damage to hair cells that otherwise occurs after transient ischemia of the cochlea.

神经干细胞（NSCs）是具有自我更新活性的多能祖细胞。最近，NSCs的使用为中枢神经系统（CNS）细胞的生成提供了一种新的策略，包括神经元、星形胶质细胞和少突胶质细胞。在这项研究中，我们评估了NSCs对沙鼠耳蜗缺血再灌注损伤的改善作用。双侧缺血性损伤1 d后，通过圆窗向一只内耳内注射NSCs；另一只耳朵作为未经治疗的对照组。巢蛋白免疫染色显示NSCs集中分布于耳蜗基底转处的Corti脏器。为了评估NSCs的移植，在移植前用表达β-半乳糖苷酶的腺病毒载体转导神经球细胞，并在移植3天后用X-gal染色证实其在耳蜗中的存在。通过连续记录听性脑干反应（ABR），比较移植侧与对照侧的听力能力。缺血第4天，与对照组相比，nsc移植侧ABR阈值的损伤性转移明显受到抑制。这些结果表明，NSCs移植在预防耳蜗短暂缺血后毛细胞损伤方面具有治疗作用。