Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, 1150 W. Med. Cntr. Dr., Ann Arbor, MI 48109-5648, USA.
Exp Neurol. 2010 Jun;223(2):464-72. doi: 10.1016/j.expneurol.2010.01.011. Epub 2010 Jan 28.
Sensory organs typically use receptor cells and afferent neurons to transduce environmental signals and transmit them to the CNS. When sensory cells are lost, nerves often regress from the sensory area. Therapeutic and regenerative approaches would benefit from the presence of nerve fibers in the tissue. In the hearing system, retraction of afferent innervation may accompany the degeneration of auditory hair cells that is associated with permanent hearing loss. The only therapy currently available for cases with severe or complete loss of hair cells is the cochlear implant auditory prosthesis. To enhance the therapeutic benefits of a cochlear implant, it is necessary to attract nerve fibers back into the cochlear epithelium. Here we show that forced expression of the neurotrophin gene BDNF in epithelial or mesothelial cells that remain in the deaf ear induces robust regrowth of nerve fibers towards the cells that secrete the neurotrophin, and results in re-innervation of the sensory area. The process of neurotrophin-induced neuronal regeneration is accompanied by significant preservation of the spiral ganglion cells. The ability to regrow nerve fibers into the basilar membrane area and protect the auditory nerve will enhance performance of cochlear implants and augment future cell replacement therapies such as stem cell implantation or induced transdifferentiation. This model also provides a general experimental stage for drawing nerve fibers into a tissue devoid of neurons, and studying the interaction between the nerve fibers and the tissue.
感觉器官通常使用受体细胞和传入神经元来转导环境信号，并将其传递到中枢神经系统。当感觉细胞丢失时，神经通常会从感觉区域退化。治疗和再生方法将受益于组织中神经纤维的存在。在听觉系统中，传入神经支配的退缩可能伴随着听觉毛细胞的退化，这与永久性听力损失有关。目前，对于严重或完全丧失毛细胞的病例，唯一的治疗方法是耳蜗植入听觉假体。为了增强耳蜗植入的治疗效果，有必要将神经纤维吸引回耳蜗上皮。在这里，我们表明，在失聪耳朵中仍然存在的上皮或间皮细胞中强制表达神经营养因子基因 BDNF，可诱导神经纤维向分泌神经营养因子的细胞强烈再生，并导致感觉区域的重新支配。神经营养因子诱导的神经元再生过程伴随着螺旋神经节细胞的显著保存。将神经纤维重新生长到基底膜区域并保护听神经的能力将增强耳蜗植入物的性能，并增强未来的细胞替代疗法，如干细胞植入或诱导转分化。该模型还为将神经纤维吸引到没有神经元的组织中，并研究神经纤维与组织之间的相互作用提供了一个通用的实验阶段。
