Adult Stem Cells in the Inner Ear

描述（由申请人提供）：存在于成人骨髓中的细胞群称为骨髓基质细胞。这种多能干细胞池易于分离，提供更新群体，并可用于自体移植。骨髓基质细胞在体内可分化为中枢和外周神经系统的神经细胞。然而，人们对骨髓基质细胞具有内耳结构中感觉神经元特性的潜力知之甚少。本研究的主要目的是测试骨髓存储细胞是否可以在发育或成人内耳中存活，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任何指导作用。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。目的#2将测试从发育中的内耳分泌的可扩散蛋白是否促进已经暴露于神经诱导信号的骨髓基质细胞的迁移或轴突生长。目的#3将测试移植的骨髓基质细胞是否可以分化并整合到成年动物或患有听神经病的动物的内耳中。将未分化或部分分化的基质细胞移植到成年正常沙鼠或用哇巴因处理的沙鼠的耳蜗中。在不同的实验条件下，将评估和比较供体基质细胞的存活、神经元分化和轴突生长的程度。总之，这些实验将提供关键信息的分化和整合的宿主耳蜗组织中的骨髓源性干细胞的因素，从而有显着的影响，在开发和实施的自体细胞替代疗法在听觉系统。

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.