Gene Therapy and Stem Cell Transplantation: Strategies for Hearing Restoration
Gene Therapy and Stem Cell Transplantation: Strategies for Hearing Restoration
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DOI：
10.1159/000218208
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Lalwani, Anil K.
中科院分区：
文献类型：
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作者：
Kesser, Bradley W.;Lalwani, Anil K.
恢复感音神经性听力损失的策略集中在替换丢失的毛细胞，Corti器官中的专门机械感受器，将声音的机械能转化为电能。哺乳动物系统中的毛细胞没有再生能力，但两项令人兴奋的研究有望恢复内耳功能。在这里，我们回顾基因治疗的基本原理，并讨论其在内耳的应用。我们调查了各种病毒载体和传递到内耳的途径。基因治疗在内耳的应用包括在面对化学或噪音诱导的耳毒性时保护毛细胞，毛细胞死亡或损伤后螺旋神经节细胞的存活，以及毛细胞再生。最近，已经报道了基因治疗在人类内耳组织中的可行性。移植能够分化成功能性毛细胞的祖细胞，并与相应的螺旋神经节细胞进行适当的连接，是恢复感音神经性听力损失的另一种策略。新生儿或胚胎干细胞、成年小鼠内耳干细胞和来自中枢神经系统的干细胞已被证明可分化为含有毛细胞标记物和蛋白质的细胞。干细胞疗法在内耳的前景，及其局限性，也将进行审查。版权所有（C）2009 S. Karger AG，巴塞尔
Strategies to restore sensorineural hearing loss focus on the replacement of lost hair cells, the specialized mechanoreceptors in the organ of Corti that convert the mechanical energy of sound into electrical energy. Hair cells in mammalian systems do not have the capacity to regenerate, but two exciting lines of research hold promise in restoring inner ear function. Here we review basic principles of gene therapy and discuss its application in the inner ear. We survey the various viral vectors and routes of delivery into the inner ear. Applications of gene therapy in the inner include hair cell protection in the face of chemical or noise-induced ototoxicity, spiral ganglion cell survival following hair cell death or injury, and hair cell regeneration. More recently, the viability of gene therapy in human inner ear tissue has been reported. Transplantation of progenitor cells that can differentiate into functioning hair cells with the appropriate connections to their corresponding spiral ganglion cells is yet another strategy to restore sensorineural hearing loss. Neonatal or embryonic stem cells, adult mouse inner ear stem cells, and stem cells from the central nervous system have been shown to differentiate into cells containing hair cell markers and proteins. Prospects for stem cell therapy in the inner ear, and its limitations, will also be examined. Copyright (C) 2009 S. Karger AG, Basel