Department of Otorhinolaryngology, Head and Neck Surgery, Hannover Medical School, Carl-Neuberg-Str 1, 30625 Hannover, Germany.
Hear Res. 2012 Jul;289(1-2):86-97. doi: 10.1016/j.heares.2012.04.007. Epub 2012 Apr 28.
The treatment of choice for profound sensorineural hearing loss (SNHL) is direct electrical stimulation of spiral ganglion cells (SGC) via a cochlear implant (CI). The number and excitability of SGC seem to be critical for the success that can be achieved via CI treatment. However, SNHL is associated with degeneration of SGC. Long-term drug delivery to the inner ear for improving SGC survival may be achieved by functionalisation of CI electrodes with cells providing growth factors. Therefore, the capacity of brain-derived neurotrophic factor (BDNF)-secreting NIH3T3 cells grown on cylindrically shaped silicone elastomers (SE) to exert local and sustained neuroprotective effects was assessed in vitro and in vivo. An in vitro model to investigate adhesion and cell growth of lentivirally modified NIH3T3 cells synthesising BDNF on SE was established. The bioactivity of BDNF was characterised by co-cultivation of SGC with cell-coated SE. In addition, cell-coated SE were implanted into deafened guinea pigs. The recombinant NIH3T3 cells proliferated on silicone surfaces during 14 days of cultivation and expressed significantly increasing BDNF levels. Enhanced survival rates and neurite outgrowth of SGC demonstrated the bioactivity of BDNF in vitro. Implantation of SE with adhering BDNF-secreting NIH3T3 cells into the cochleae of systemically deafened guinea pigs induced a significant increase in SGC survival in comparison to SE without cell coating. Our data demonstrate a novel approach of cell-based long-term drug delivery to support SGC survival in vitro and in vivo. This therapeutic strategy--once transferred to cells suitable for clinical application--may improve CI performance.
对于深度感音神经性听力损失（SNHL），首选的治疗方法是通过人工耳蜗（CI）直接刺激螺旋神经节细胞（SGC）。SGC 的数量和兴奋性似乎对通过 CI 治疗可以实现的成功至关重要。然而，SNHL 与 SGC 的变性有关。通过将提供生长因子的细胞功能化来实现内耳的长期药物输送以改善 SGC 存活的可能性。因此，在体外和体内评估了在圆柱状硅酮弹性体（SE）上生长的分泌脑源性神经营养因子（BDNF）的 NIH3T3 细胞对 SGC 发挥局部和持续神经保护作用的能力。建立了一种体外模型，用于研究在 SE 上合成 BDNF 的慢病毒修饰 NIH3T3 细胞的粘附和细胞生长。通过与细胞包被的 SE 共培养来表征 BDNF 的生物活性。此外，将细胞包被的 SE 植入耳聋豚鼠。转染的 NIH3T3 细胞在培养的 14 天内在硅酮表面增殖，并表达出显著增加的 BDNF 水平。体外增强的 SGC 存活率和神经突生长表明 BDNF 具有生物活性。与没有细胞涂层的 SE 相比，将粘附有分泌 BDNF 的 NIH3T3 细胞的 SE 植入全身耳聋豚鼠的耳蜗中，可显著增加 SGC 的存活率。我们的数据证明了一种新的基于细胞的长期药物输送方法，可支持体外和体内 SGC 的存活。这种治疗策略一旦转移到适合临床应用的细胞上，就可能改善 CI 的性能。
