Abstract:
The incidence and prevalence of hearing loss is increasing globally at an accelerated pace. Hair cells represent the sensory receptors of auditory and vestibular systems. Hair cell absence, loss or degeneration due to congenital diseases, trauma, toxicity, infection or advancing age, results in disabling hearing loss. Regenerative medicine approaches consisting in stem cell-based hair cell rescue or regeneration, gene therapy, as well as cell and tissue engineering are expected to dramatically improve the therapeutic arsenal available for addressing hearing loss. Current strategies that are using different stem cell types to rescue or to induce hair cell proliferation and regeneration are presented. Gene and cell therapy methods that modulates transdifferentiation of surrounding cell types into hair cells are presented, together with their specific advantages and limitations. Several modalities for improving therapeutic targeting to the inner ear such as nanoparticle-mediated cell and gene delivery are introduced. Further steps in building more relevant high-throughput models for testing novel drugs and advanced therapies are proposed as a modality to accelerate translation to clinical settings.
摘要:
听力损失的发生率和患病率在全球范围内以加速的速度增加。毛细胞代表听觉和前庭系统的感觉受体。毛细胞缺失,由于先天性疾病而导致的损失或退化,创伤,毒性,感染或年龄增长,导致听力损失。再生医学方法包括基于干细胞的毛细胞拯救或再生,基因治疗,以及细胞和组织工程有望显着改善可用于解决听力损失的治疗库。提出了使用不同干细胞类型来挽救或诱导毛细胞增殖和再生的当前策略。提出了调节周围细胞类型转分化为毛细胞的基因和细胞治疗方法,以及它们的特定优势和局限性。介绍了几种用于改善对内耳的治疗靶向的方式,例如纳米颗粒介导的细胞和基因递送。提出了建立更多相关的高通量模型以测试新药和先进疗法的进一步步骤,作为加速向临床环境转化的方式。