Auditory Stem Cell Transplantation and Cochlear Implants in Animal Models of Deafness

耳聋动物模型中的听觉干细胞移植和人工耳蜗植入

• 批准号: G0900919/1
• 负责人: Marcelo Rivolta
• 金额: $ 73.96万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900919%2F1
• 关键词: Auditory; Stem; Cell; Transplantation; Cochlear

Hearing loss is a main public health issue, with more than 250 million people affected worldwide. The vast majority of these cases are produced by the damage of two critical cells of the hearing pathway, the sensory hair cells and the auditory neurons located in the cochlea. Hair cells can ?sense? sound by detecting small vibrations through the movement of the tiny ?hairs? located at their top. This movement is translated into electrical signals that are sent to the auditory neurons, which in turn take the information to the brain. While birds have the ability to regenerate and replace hair cells, mammals in general and humans in particular have lost this ability. Sensory hair cells and neurons are only produced in the womb during development, making their loss permanent and deafness irreversible. At the moment, no medical treatment is available for the condition. However, in severe cases, the function of the lost hair cells can be replaced by a prosthetic device, the cochlear implant. The cochlear implant, however, can only work provided the auditory neurons are preserved. In many patients this is not the case and cochlear implantation is not possible. Even worst, since it is difficult to judge the quality of the neurons beforehand, some patients are implanted only to have their hopes shattered by a poor performance and little or no recovery of hearing. In this project, we want to explore if, by using stem cells, we could replace the damaged neurons and enhance the efficacy and applicability of cochlear implants in the treatment of deafness. Our laboratory has already succesfully isolated populations of human stem cells that have the capacity to produce sensory neurons in a test tube. Now, we want to use them toghether with cochlear implants, to treat animals that have a deafness similar to that which will lead to a cochlear implant failure in humans. We want to see if the transplanted cells will establish connections with the electrical electrodes and eventually, produce a functional recovery. If succesful, these findings could pave the way to offer a solution to thousands of patients that cannot be helped today with conventional cochlear implants.

听力损失是一个主要的公共卫生问题，全世界有超过2.5亿人受到影响。这些病例中的绝大多数是由听觉通路的两个关键细胞，即位于耳蜗中的感觉毛细胞和听觉神经元的损伤引起的。毛细胞可以吗？有意义吗？声音通过检测微小的振动通过运动的微小？头发？位于其顶部。这种运动被转化为电信号，发送到听觉神经元，听觉神经元又将信息传递到大脑。虽然鸟类有再生和替换毛细胞的能力，但哺乳动物，特别是人类，已经失去了这种能力。感觉毛细胞和神经元只在发育过程中在子宫中产生，这使得它们的永久性丧失和耳聋不可逆转。目前，这种情况没有任何治疗方法。然而，在严重的情况下，失去的毛细胞的功能可以通过人工耳蜗植入装置来替代。然而，人工耳蜗只有在保留听觉神经元的情况下才能工作。在许多患者中，情况并非如此，人工耳蜗植入是不可能的。更糟糕的是，由于很难事先判断神经元的质量，一些患者被植入后，他们的希望只被糟糕的表现和很少或根本没有恢复听力所破灭。在这个项目中，我们希望探索是否可以通过使用干细胞来替代受损的神经元，并提高人工耳蜗植入治疗耳聋的有效性和适用性。我们的实验室已经成功地分离出了人类干细胞群，这些细胞能够在试管中产生感觉神经元。现在，我们想把它们和人工耳蜗一起使用，来治疗动物的耳聋，这些动物的耳聋类似于人类人工耳蜗植入失败的原因。我们想看看移植的细胞是否会与电极建立连接，并最终产生功能恢复。如果成功的话，这些发现可以为成千上万的患者提供解决方案铺平道路，这些患者今天无法通过传统的人工耳蜗植入物获得帮助。