再生的回响：重建哺乳动物内耳

文献信息

中文摘要

背景： 听力损失和眩晕是全世界最常见的感觉障碍。约5%的世界人口受到致残性听力损失的影响，并且预计其患病率将在未来几十年内增加。耳蜗毛细胞对于将声音振动转换为电信号至关重要，这些电信号随后通过螺旋神经节神经元传递至中枢并导致声音感知。耳蜗毛细胞的不可逆丢失是人类感音神经性听力损失最常见的病理基础。与之形成鲜明对比的是，鸡和斑马鱼等非哺乳动物物种在毛细胞损伤后能够从内源性支持细胞自发再生毛细胞，并且这一过程的机制正开始被揭示。对内耳毛细胞发育理解的进展已导致能够高效生成小鼠和人类内耳类器官的新方案。最近已建立了若干新的、有前景的重编程方法，以在成熟小鼠耳蜗和前庭器官中诱导毛细胞再生。在这篇综述中，我们将讨论这些最新进展、对人类听力损失和平衡功能障碍治疗的意义，以及该领域的未来方向。

英文摘要

Hearing loss and dizziness are the most common sensory disorders worldwide. About 5% of the world's population is affected by disabling hearing loss, and the prevalence is projected to increase over the next several decades. Cochlear hair cells are essential in converting sound vibrations into electrical signals, which are then relayed centrally via the spiral ganglion neurons and lead to sound perception. The irreversible loss of cochlear hair cells is the most common pathology underlying sensorineural hearing loss in humans. In stark contrast, nonmammalian species such as chicken and zebrafish spontaneously regenerate hair cells from endogenous supporting cells after hair cell damage, and the mechanisms of this process are starting to be revealed. Advances in the understanding of inner ear hair cell development have led to novel protocols to efficiently generate mouse and human inner ear organoids. Several new and promising reprogramming approaches have recently been established to induce hair cell regeneration in the mature mouse cochlear and vestibular organs. In this review, we will discuss these recent advances, the implications for treatments for human hearing loss and balance dysfunction, and future directions of the field.