Regenerating hair cells in the mammalian inner ear: defining conditions in the vestibular sensory epithelia.

平衡功能障碍会导致头晕和眩晕。它经常致残，是老年人跌倒的重要原因。头晕是老年人去看全科医生最常见的原因。它也普遍存在于后天性耳聋的人群中。平衡功能障碍的一个主要因素是感觉毛发的丧失。来自内耳前庭（平衡）系统的细胞。这项研究将评估在前庭系统再生毛细胞的潜力。从人类、幼鼠和老年小鼠身上提取的前庭组织将在培养中保存。一个由全英国耳鼻喉外科医生组成的联盟将提供人类前庭组织，这些组织通常在听神经瘤（听神经的良性肿瘤）手术中被丢弃。这为动物和人类内耳组织的直接实验比较提供了一个独特的机会。当毛细胞死亡时，每个毛细胞周围的支持细胞会关闭病变。有证据表明，在失去毛细胞后，支持细胞有时会转化为毛细胞，以取代失去的毛细胞。该项目将比较在插入基因Atoh1后，这些前庭组织中再生功能性毛细胞的能力，该基因已知可诱导支持细胞转化为毛细胞，当由含有该基因的非毒性病毒将其传递给支持细胞时。该项目还将评估通过药物操纵内耳发育过程中通常活跃的生化途径来诱导支持细胞转化的可能性，以调节前体细胞（如毛细胞或支持细胞）的不同命运。也有证据表明，老鼠的前庭系统含有少量干细胞，可以从中产生毛细胞。该项目将检查人类前庭感觉组织中是否存在这样的细胞群，如果存在，这些细胞是否可以提供替代毛细胞的替代来源。然而，任何成功的毛细胞替代策略都依赖于毛细胞丢失后保留的支持细胞维持一个支持功能性替代毛细胞存活的环境。因此，该项目还将确定毛细胞丢失后恢复期间支持细胞群的特征，以确定再生发生的条件。确定前庭系统中毛细胞再生的条件将导致对广泛致残状况的临床治疗。

Balance dysfunction results in dizziness and vertigo. It is often disabling and is a significant contributor to falls in the elderly. Dizziness is the most common cause of visits to the GP amongst the elderly population. It is also prevalent amongst those with acquired deafness. One major factor underlying balance dysfunction is the loss of sensory ?hair? cells from the vestibular (balance) system in the inner ear. This study will assess the potential for regenerating hair cells in the vestibular system. Vestibular tissue taken from humans and from young and aged mice will be maintained in culture. A consortium of ENT surgeons across the UK will provide human vestibular tissue, normally discarded during surgery for acoustic neuromas (benign tumours of the auditory nerve). This presents a unique opportunity for direct experimental comparison of inner ear tissues of animals and humans. When hair cells die the supporting cells that surround each one close the lesions. There is some evidence that after loss of hair cells, supporting cells can sometimes convert into hair cells, to replace those lost. This project will compare the capacity to regenerate functional hair cells in these vestibular tissues after insertion of a gene, Atoh1, that is known to induce conversion of supporting cells into hair cells, when delivered to supporting cells by a non-virulent virus engineered to contain it. The project will also assess possibilities for inducing supporting cell conversion by pharmacological manipulation of a biochemical pathway that normally is active during development of the inner ear to regulate the differential fate of precursor cells as hair cells or supporting cells. There is also evidence that the vestibular system of mice contains a small population of stem cells from which hair cells can be generated. The project will examine whether such a population exists in the human vestibular sensory tissues, and if so whether such cells could provide an alternative source of replacement hair cells. Any successful hair cell replacement strategy, however, depends upon the supporting cells that remain after hair cell loss maintaining an environment that will support the survival of functional replacement hair cells. The project therefore will also identify the characteristics of the supporting cell population during recovery after hair cell loss to determine the conditions under which regeneration occurs. Defining the conditions for hair cell regeneration in the vestibular system will lead to clinical treatments for a wide-spread, disabling condition.