Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Sci Rep. 2024 Jul 10;14(1):15903. doi: 10.1038/s41598-024-66635-4.
Losing either type of cochlear sensory hair cells leads to hearing impairment. Inner hair cells act as primary mechanoelectrical transducers, while outer hair cells enhance sound-induced vibrations within the organ of Corti. Established inner ear damage models, such as systemic administration of ototoxic aminoglycosides, yield inconsistent and variable hair cell death in mice. Overcoming this limitation, we developed a method involving surgical delivery of a hyperosmotic sisomicin solution into the posterior semicircular canal of adult mice. This procedure induced rapid and synchronous apoptotic demise of outer hair cells within 14 h, leading to irreversible hearing loss. The combination of sisomicin and hyperosmotic stress caused consistent and synergistic ototoxic damage. Inner hair cells remained until three days post-treatment, after which deterioration in structure and number was observed, culminating in a complete hair cell loss by day seven. This robust animal model provides a valuable tool for otoregenerative research, facilitating single-cell and omics-based studies toward exploring preclinical therapeutic strategies.
丧失任何一种耳蜗感觉毛细胞都会导致听力损伤。内毛细胞作为主要的机电换能器，而外毛细胞则增强了耳蜗内的声音诱导振动。已建立的内耳损伤模型，如全身性给予耳毒性氨基糖苷类药物，在小鼠中产生不一致和可变的毛细胞死亡。为了克服这一限制，我们开发了一种方法，将高渗西索米星溶液通过手术递送至成年小鼠的后半规管。该方法在 14 小时内诱导外毛细胞快速而同步的凋亡，导致不可逆的听力损失。西索米星和高渗应激的组合导致一致且协同的耳毒性损伤。内毛细胞在治疗后三天仍然存在，之后观察到结构和数量的恶化，最终在第七天导致毛细胞完全丧失。这种强大的动物模型为耳再生研究提供了一个有价值的工具，促进了单细胞和组学研究，以探索临床前治疗策略。
