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

神经干细胞(NSCs)是具有自我更新能力的多能祖细胞。最近，神经干细胞的使用为中枢神经系统(CNS)细胞的产生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。在本研究中，我们评估了神经干细胞在改善沙土鼠耳蜗骨缺血再灌注损伤中的作用。双侧脑缺血损伤后1天，一侧内耳通过圆窗注入神经干细胞，另一耳作为未处理的对照。Nestin免疫组织化学染色显示，NSCs的分布集中在耳蜗底转处的Corti器。为了评价神经干细胞的植入情况，在移植前用表达β-半乳糖苷酶的腺病毒载体转导神经干细胞，移植后3d用X-Gal染色证实其存在于耳蜗内。通过连续记录听性脑干反应(ABR)，比较移植侧和对照侧的听力。在缺血第4天，神经干细胞移植侧与对照侧相比，损伤引起的ABR阈值漂移明显受到抑制。这些结果表明，神经干细胞移植在治疗上是有用的，以防止毛细胞损伤，否则发生在耳蜗一过性缺血后。

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.