Hildebrand Michael S, Newton Stephen S, Gubbels Samuel P, Sheffield Abraham M, Kochhar Amit, de Silva Michelle G, Dahl Hans-Henrik M, Rose Scott D, Behlke Mark A, Smith Richard J H
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
Mol Ther. 2008 Feb;16(2):224-36. doi: 10.1038/sj.mt.6300351. Epub 2007 Nov 27.
Development of effective therapeutics for hearing loss has proven to be a slow and difficult process, evidenced by the lack of restorative medicines and technologies currently available to the otolaryngologist. In large part this is attributable to the limited regenerative potential in cochlear cells and the secondary degeneration of the cochlear architecture that commonly follows sensorineural hearing impairment. Therapeutic advances have been made using animal models, particularly in regeneration and remodeling of spiral ganglion neurons, which retract and die following hair cell loss. Natural regeneration in avian and reptilian systems provides hope that replacement of hair cells is achievable in humans. The most exciting recent advancements in this field have been made in the relatively new areas of cellular replacement and gene therapy. In this review we discuss recent developments in gene- and cell-based therapy for hearing loss, including detailed analysis of therapeutic mechanisms such as RNA interference and stem cell transplantation, as well as in utero delivery to the mammalian inner ear. We explore the advantages and limitations associated with the use of these strategies for inner ear restoration.
事实证明，开发有效的听力损失治疗方法是一个缓慢而艰难的过程，目前耳鼻喉科医生可用的恢复性药物和技术匮乏就证明了这一点。在很大程度上，这归因于耳蜗细胞有限的再生潜力以及感音神经性听力障碍后常见的耳蜗结构继发性退化。利用动物模型已取得了治疗进展，特别是在螺旋神经节神经元的再生和重塑方面，这些神经元在毛细胞损失后会退缩并死亡。鸟类和爬行类系统中的自然再生让人们看到了在人类身上实现毛细胞替代的希望。该领域最近最令人兴奋的进展是在相对较新的细胞替代和基因治疗领域取得的。在这篇综述中，我们讨论了用于听力损失的基因治疗和细胞治疗的最新进展，包括对RNA干扰和干细胞移植等治疗机制的详细分析，以及向哺乳动物内耳的子宫内递送。我们探讨了使用这些策略进行内耳修复的优点和局限性。
