Adult Stem Cells in the Inner Ear

描述（由申请人提供）：居住在成人骨髓中的是一种称为骨髓基质细胞的细胞群。这种多能干细胞池易于分离，提供了一个更新的群体，可用于自体移植。骨髓基质细胞在体内可分化为中枢和周围神经系统的神经元细胞。然而，对于骨髓基质细胞是否具有内耳结构中感觉神经元的特性，我们所知甚少。本研究的主要目的是测试骨髓基质细胞是否能够在发育或成体内耳中存活、分化和建立连接，以及微环境分泌的信号蛋白是否在这些过程中发挥指导作用。目的1将测试骨髓基质细胞和发育中的内耳周围组织之间的相互作用是否在组织特异性神经元分化中起指导作用。Aim #2将测试发育中的内耳分泌的扩散蛋白是否促进了暴露于神经诱导信号的骨髓基质细胞的迁移或轴突生长。Aim #3将测试移植的骨髓基质细胞是否能够分化并整合到成年动物或患有听神经病变的动物的内耳中。未分化或部分分化的间质细胞将被移植到成年正常沙鼠或经瓦巴因治疗的沙鼠耳蜗中。在不同的实验条件下，评估和比较供体基质细胞的存活程度、神经元分化程度和轴突生长情况。总之，这些实验将为宿主耳蜗组织中骨髓干细胞分化和整合的关键因素提供重要信息，因此对听觉系统中自体细胞替代疗法的发展和实施具有重要意义。

DESCRIPTION (provided by applicant): Resident in adult bone marrow is a cell population called the marrow stromal cells. This pool of pluripotent stem cells is easy to isolate, provides a renewal population and can be used for autologous transplantation. Marrow stromal cells have been shown to differentiate into neuronal cells in the central and peripheral nervous systems in vivo. Little, however, is known about the potential of marrow stromal cells to take on properties of sensory neurons residing in the inner ear structures. The primary goal of this study is to test whether marrow storomal cells can survive, differentiate and establish connectivity within the developing or adult inner ear, and whether signaling proteins secreted from the microenvironment play any instructive roles in these processes. Aim #1 will test whether interactions between marrow stromal cells and tissues surrounding the developing inner ear play an instructive role in tissue-specific neuronal differentiation. Aim #2 will test whether diffusible proteins secreted from the developing inner ear promote migration or axon outgrowth of marrow stromal cells that have been exposed to neural induction signals. Aim #3 will test whether transplanted marrow stromal cells can differentiate and integrate into the inner ear of adult animals or animals with auditory neuropathy. Undifferentiated or partially-differentiated stromal cells will be transplanted into the cochlea of adult normal gerbils or gerbils treated with ouabain. The extent of survival, neuronal differentiation and axon outgrowth of donor stromal cells will be evaluated and compared among different experimental conditions. Together, these experiments would provide critical information on factors essential for the differentiation and integration of bone marrow-derived stem cells in the host cochlear tissue, and thus have significant implications in the development and implementation of an autologous cell replacement therapy in the auditory system.