通过细胞疗法增强听神经功能——现状、手术入路和潜在候选者。

文献信息

中文摘要

背景： 即使手术在技术上成功且康复充分，人工耳蜗植入后言语感知不佳仍是一个重要的临床问题。这种异质性的“表现不佳者”表型可能单独或合并反映设备、电极、认知、中枢听觉或神经因素。功能健全的听神经是人工耳蜗（CI）获益的必要条件，然而死后研究并未显示绝对螺旋神经节神经元（SGN）计数与言语识别之间存在一致关系。这表明，在许多患者中，限制因素可能是神经功能而非单纯的神经元数量，并且当功能性听觉神经元丢失本身是主要且可能可治疗的病变时，耳神经祖细胞（ONP）细胞疗法最为合理。本综述评估了SGN完整性与CI结局相关的证据，提出了识别ONP治疗候选者的分阶段框架，评价了神经功能的电生理测量方法，并综述了将细胞递送至人类耳蜗的手术入路。结论：尸体和临床前研究支持手术递送的技术可行性，但当前的电生理工具仅提供间接的、主要是个体内信息，尚无单一经过验证的测量方法能够以试验纳入所需的特异性识别个体中的SGN变性。最终，临床获益将取决于持久的细胞存活、正确的分化和连接，以及与CI刺激的功能整合。因此，ONP疗法代表一种有前景但仍处于研究阶段的策略，其通往临床的路径将取决于严格的患者分层、经过验证的诊断和结局测量，以及对长期安全性和有效性的明确证明。

英文摘要

Poor speech perception after cochlear implantation remains an important clinical problem, even when surgery is technically successful and rehabilitation is adequate. This heterogeneous "poor performer" phenotype can reflect device, electrode, cognitive, central-auditory, or neural factors, alone or in combination. A functionally competent auditory nerve is necessary for cochlear implant (CI) benefit, yet post-mortem studies have not shown a consistent relationship between absolute spiral ganglion neuron (SGN) counts and speech recognition. This suggests that neural function, rather than neuron number alone, is likely to be the limiting factor in many patients, and that otic neural progenitor (ONP) cell therapy is most plausible when loss of functional auditory neurons is itself the dominant, potentially treatable lesion. This review evaluates the evidence linking SGN integrity to CI outcomes, proposes a staged framework for identifying candidates for ONP therapy, appraises electrophysiological measures of neural function, and surveys surgical approaches for delivering cells to the human cochlea. Cadaveric and preclinical studies support the technical feasibility of surgical delivery, but current electrophysiological tools provide only indirect, largely within-patient information, and no single validated measure can yet identify SGN degeneration in an individual with the specificity required for trial inclusion. Ultimately, clinical benefit will depend on durable cell survival, correct differentiation and connectivity, and functional integration with CI stimulation. ONP therapy therefore represents a promising but still investigational strategy, whose path to the clinic will depend on rigorous patient stratification, validated diagnostic and outcome measures, and clear demonstration of long-term safety and efficacy.