Stem-cell therapy for hearing loss: are we there yet?

Abstract Introduction: Mammalian hair cells and auditory neurons do not show regenerative capacity. Hence, damage to these cell types is permanent and leads to hearing loss. However, there is no treatment that re-establishes auditory function. Regenerative therapies using stem cells represent a promising alternative. Objective: This article aims to review the current literature about the main types of stem cells with potential for application in cell therapy for sensorineural hearing loss, the most relevant experiments already performed in animals, as well as the advances that have been recently made in the field. Methods: Research included the databases PubMed/MEDLINE, Web of Science, Science Direct and SciELO, as well as gray literature. Search strategy included the following main terms: "stem cells", "hair cells" and "auditory neurons". Additionally, the main terms were combined with the following secondary terms: "mesenchymal", "iPS", "inner ear", "auditory". The research was conducted independently by three researchers. Results: Differentiation of stem cells into hair cells and auditory neurons has a high success rate, reaching up to 82% for the first and 100% for the latter. Remarkably, these differentiated cells are able to interact with hair cells and auditory neurons of cochlear explants through formation of new synapses. When transplanted into the cochlea of animals with hearing loss, auditory restoration has been documented to date only in deafferented animals. Conclusion: Advances have been more prominent in cases of auditory neuropathy, since partial improvement of auditory nerve conditions through cell-based therapy may increase the number of patients who can successfully receive cochlear implants.

**引言与摘要**：哺乳动物毛细胞（hair cells）与听觉神经元（auditory neurons）不具备再生能力。因此，此类细胞的损伤将为永久性损伤，并会引发听力损失。目前尚无能够恢复听觉功能的治疗手段，而基于干细胞（stem cells）的再生疗法则是极具潜力的替代方案。
**研究目的**：本文旨在综述当前相关文献，内容涵盖有望应用于感音神经性听力损失细胞疗法的主要干细胞类型、已在动物模型中开展的最具相关性的实验，以及该领域近期取得的研究进展。
**研究方法**：本次文献检索涵盖PubMed/MEDLINE、Web of Science、Science Direct及SciELO数据库，同时纳入灰色文献。检索策略采用的核心检索词包括‘干细胞’‘毛细胞’与‘听觉神经元’；此外，将核心检索词与‘间充质（mesenchymal）’‘iPS’‘内耳（inner ear）’及‘听觉’进行组合检索。本次检索由三名研究人员独立完成。
**研究结果**：干细胞向毛细胞与听觉神经元的分化成功率较高，其中向毛细胞的分化成功率可达82%，向听觉神经元的分化成功率则可达100%。值得注意的是，此类分化后的细胞可通过形成新突触，与耳蜗外植体的毛细胞及听觉神经元建立相互作用。当将此类细胞移植至听力损失动物的耳蜗内时，截至目前仅在去传入动物中观察到了听觉功能恢复的相关记录。
**研究结论**：该领域在听神经病相关研究中进展更为显著，这是因为通过细胞疗法对听觉神经状态进行部分改善，可增加能够成功接受人工耳蜗植入的患者数量。