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（NSC）是具有自我更新活性的多能祖细胞，最近使用 NSC 为中枢神经系统（CNS）细胞（包括神经元、星形胶质细胞和少突胶质细胞）的产生提供了新的策略。在一项研究中，我们评估了 NSCs 在改善沙鼠耳蜗缺血再灌注损伤方面的效用，NSCs 通过圆窗注射到一只内耳中。双侧缺血性损伤后的第二天；另一只耳朵作为未处理的对照，巢蛋白的免疫染色显示，NSC 的分布集中在耳蜗基底转的 Corti 器官中，用腺病毒转导了神经球细胞。移植前表达β-半乳糖苷酶的载体，并在移植后3天使用X-gal染色证明它们在耳蜗中的存在。通过连续记录听性脑干反应（ABR），将移植侧与对照侧进行比较，在缺血的第四天，损伤引起的 ABR 阈值变化在 NSC 移植侧明显受到抑制。这些结果表明，神经干细胞移植对于预防耳蜗短暂缺血后发生的毛细胞损伤具有治疗作用。