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自体线粒体移植可增强听觉细胞的生物能量代谢,并减轻由庆大霉素诱导的细胞损失。

Autologous mitochondrial transplantation enhances the bioenergetics of auditory cells and mitigates cell loss induced by HO.

作者信息

Okur Mustafa Nazir, Ratajczak Adam, Kheradvar Arash, Djalilian Hamid R

机构信息

Department of Otolaryngology-Head and Neck Surgery, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.

Department of Biomedical Engineering, University of California, 2420 Engineering Hall, Irvine, CA,92697-2730, USA.

出版信息

Mitochondrion. 2025 Mar;81:102003. doi: 10.1016/j.mito.2024.102003. Epub 2024 Dec 25.

Abstract

Hearing loss is a widespread and disabling condition with no current cure, underscoring the urgent need for new therapeutic approaches for treatment and prevention. A recent mitochondrial therapy approach by introducing exogenous mitochondria to the cells has shown promising results in mitigating mitochondria-related disorders. Despite the essential role of mitochondria in hearing, this novel strategy has not yet been tested for the treatment of hearing loss. More importantly, whether cochlear cells take up exogenous mitochondria and its consequence on cell bioenergetics has never been tested before. Here, we showed that exogenous mitochondria from HEI-OC1 auditory cells internalize into a new set of HEI-OC1 cells through co-incubation in a dose-dependent manner without inducing toxicity. We observed that auditory cells that received exogenous mitochondria exhibited increased bioenergetics compared to the controls that received none. Furthermore, we found that mitochondrial transplantation protects cells from oxidative stress and HO-induced apoptosis, while partially restoring bioenergetics diminished by HO exposure. These findings support initial evidence for the feasibility and potential advantages of mitochondrial therapy in auditory cells. If successful in animal models and ultimately in humans, this novel therapy offers prominent potential for the treatment of sensorineural hearing loss.

摘要

听力损失是一种普遍存在且使人致残的疾病,目前尚无治愈方法,这凸显了对治疗和预防新疗法的迫切需求。最近一种通过将外源性线粒体引入细胞的线粒体治疗方法,在减轻线粒体相关疾病方面已显示出有前景的结果。尽管线粒体在听力中起着至关重要的作用,但这种新策略尚未在听力损失治疗中进行测试。更重要的是,耳蜗细胞是否摄取外源性线粒体及其对细胞生物能量学的影响此前从未被测试过。在此,我们表明,来自HEI-OC1听觉细胞的外源性线粒体通过共孵育以剂量依赖的方式内化到一组新的HEI-OC1细胞中,且不会诱导毒性。我们观察到,与未接受外源性线粒体的对照组相比,接受外源性线粒体的听觉细胞表现出生物能量学增加。此外,我们发现线粒体移植可保护细胞免受氧化应激和HO诱导的细胞凋亡,同时部分恢复因HO暴露而减少的生物能量学。这些发现为线粒体治疗在听觉细胞中的可行性和潜在优势提供了初步证据。如果在动物模型中取得成功并最终应用于人类,这种新疗法在治疗感音神经性听力损失方面具有显著潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a369/12090353/be73e5e61e27/nihms-2064711-f0002.jpg

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