干细胞治疗听力损失的研究进展

文献信息

中文摘要

背景： 听力损失是最常见的感觉障碍，对语言发育、读写能力、情绪和认知造成重大影响。感音神经性听力损失由耳蜗毛细胞、耳蜗神经或中枢听觉通路损伤引起，占听力损失的大多数病例。现有的感音神经性听力损失治疗方法包括助听器和人工耳蜗；然而，这些方法在噪声环境中的效果有限，听力结果可变，且频率分辨能力有限。目前尚无美国食品药品监督管理局批准的细胞、分子或药理学疗法可用。干细胞疗法是一种新兴且有前景的治疗感音神经性听力损失的方法，通过将外源性干细胞移植到耳蜗中。基于干细胞的内耳系统对于研究干细胞如何模拟或恢复内耳功能至关重要。二维培养系统有助于理解内耳神经上皮中多能干细胞的分化。然而，它们无法模拟组织特异性结构和特定的细胞相互作用。研究人员随后转向开发三维内耳类器官的分化方案，这些类器官更接近体内结构。这些方法是在开发针对耳蜗中再生能力有限或没有再生能力的结构（包括毛细胞、螺旋神经节神经元和螺旋韧带纤维细胞）的干细胞疗法方面有希望的一步。该领域的未来方向包括将干细胞疗法与基因治疗方法相结合，并开发新型高通量药物筛选平台。

英文摘要

Hearing loss is the most common sensory disorder, causing substantial impacts on language development, literacy, mood, and cognition. Sensorineural hearing loss, caused by injury to the cochlear hair cells, cochlear nerve, or central auditory pathways, accounts for most cases of hearing loss. Existing therapies for sensorineural hearing loss include hearing aids and cochlear implants; however, these modalities have limited efficacy in noisy environments, variable hearing outcomes, and limited frequency discrimination. There are currently no Food and Drug Administration-approved cellular, molecular, or pharmacological therapies available. Stem cell therapy is an emerging and promising approach to treating sensorineural hearing loss through transplanting exogenous stem cells into the cochlea. Stem cell-based inner ear systems have been crucial to studying how stem cells can mimic or restore the function of the inner ear. The two-dimensional culture system has been instrumental in understanding pluripotent stem cell differentiation in the inner ear neuroepithelium. However, they are unable to mimic tissue-specific architecture and specific cellular interactions. Researchers subsequently moved to develop differentiation protocols in three-dimensional inner ear organoids, which more closely resemble in vivo structures. Such approaches are a promising step forward in the development of stem cell therapies focusing on structures in the cochlea that have limited to no ability to regenerate, including hair cells, spiral ganglion neurons, and spiral ligament fibrocytes. Future directions of this field include integrating stem cell therapy with gene therapy approaches and developing novel high-throughput drug screening platforms.