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

听力损失是一个主要的公共卫生问题，全球有超过2.5亿人受到影响。这些病例中的绝大多数是由于听力通路的两个关键细胞--位于耳蜗处的感觉毛细胞和听觉神经元--的损伤造成的。毛细胞能感觉到吗？通过微小毛发的运动来检测微小的振动来发出声音？位于它们的顶端。这种运动被转化为电信号，并被发送到听觉神经元，而听觉神经元又将信息传递给大脑。虽然鸟类具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子宫发育过程中产生，使它们永久丧失，耳聋不可逆转。目前，还没有针对这种情况的治疗方法。然而，在严重的情况下，失去的毛细胞的功能可以被假体设备--人工耳蜗--所取代。然而，只有在听觉神经元得到保护的情况下，人工耳蜗才能发挥作用。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，他们的希望只因表现不佳和听力几乎或根本没有恢复而破灭。在这个项目中，我们想要探索，通过使用干细胞，我们是否可以取代受损的神经元，并增强人工耳蜗在耳聋治疗中的有效性和适用性。我们的实验室已经成功分离出有能力在试管中产生感觉神经元的人类干细胞群体。现在，我们希望将它们与人工耳蜗一起使用，用于治疗耳聋的动物，这些动物的耳聋与导致人类人工耳蜗植入失败的耳聋相似。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，这些发现可能为数以千计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。

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.