TISSUE ENGINEERING OF THE INNER EAR

在过去的几年里，有三个重要的发现对听觉系统受损的治疗具有重要意义。首先，成年动物耳聋会导致外周听觉系统发生显着变化。第二，这些变化影响耳聋后输入的重新引入。第三，现在可以干预和影响与健康有关的变化，以允许对重新引入的输入进行最佳处理。这种干预措施可以被称为“组织工程”和他们的基础发展，并应用驱动我们提出的研究。我们目前关于可能影响感觉神经的存活和功能的干预措施的大量知识来自培养和器官型制剂中细胞的体外研究。本研究的目的是验证这些干预措施在体内的有效性，并测试潜在干预措施的有效性和安全性，以“工程”内耳组织在体内。我们的第一个具体目标是测试的效用和协同作用的化学和活性因子参与的听觉神经的生存增强螺旋神经节存活后耳聋。我们假设有多种因素参与螺旋神经节细胞的维持，这不仅提供了冗余（增加保护），而且还具有协同作用，我们可以用多种因素实现最大的增强。我们的第二组研究如何神经营养因子和刺激诱导的活动不仅可以增强螺旋神经节细胞的存活，而且还诱导听神经外周突的再生，内毛细胞损失后退化。我们的最终目标是开发知识库和工具，以干预和影响受损的听觉系统，为听觉信息的重新引入提供尽可能好的环境。希望这些体内研究将为该技术向人类应用的转移提供关键的一步。开发的干预措施将为将来重新连接再生毛细胞提供必要的基质。这将直接提高目前人工耳蜗的效益。

Three critical findings have been made over the last several years with important implications to the treatment of the deafened auditory system. First, there are significant changes to the peripheral auditory system as a consequence of deafness in the adult animal. Second, these changes impact on the reintroduction of input after deafness. Third, it is now possible to intervene and influence deafness-related changes to permit optimal processing of re-introduced input. Such interventions can be termed "Tissue Engineering" and their basis development, and application drive our proposed studies. A great deal of our current knowledge regarding interventions that may effect the survival and function of the sensory nerves derives from in vitro studies of cells in culture and organotypic preparations. The goal of this investigation is to verify the validity of these interventions in vivo, and to test the efficacy and safety of potential interventions to "engineer" the tissues of the inner ear in vivo. Our first specific aim is to test the utility and synergy of chemical and activity factors involved in the survival of the auditory nerve for enhanced spiral ganglion survival after deafness. We hypothesize that there are naturally multiple factors involved in the maintenance of spiral ganglion cells, which not only provides redundancy (for increased protection) but also synergy in effect, and we can achieve maximal enhancement with multiple factors. Our second set of studies how neurotrophic factors and stimulation induced activity can not only enhance spiral ganglion cell survival but also induce regrowth of auditory nerve peripheral process, which regress after inner hair cell loss. Our ultimate goal is to develop the knowledge base and the tools to intervene in and influence the deafened auditory system to provide the best possible environment for re-introduction of auditory information. Hopefully, these in vivo studies will provide a critical step in the transfer of this technology to human application. The interventions that are developed will provide the substrate essential for reconnecting regenerated hair cells in the future. The should directly enhance the benefit of cochlear prostheses at present.