Adult Stem Cells in the Inner Ear

描述(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。这个多能干细胞库很容易分离，提供更新的种群，并可用于自体移植。体内研究表明，骨髓基质细胞在中枢和外周神经系统中可分化为神经细胞。然而，关于骨髓基质细胞具有驻留在内耳结构中的感觉神经元的特性的潜力，人们知之甚少。这项研究的主要目的是测试骨髓干细胞是否能够在发育中的内耳或成年内耳内存活、分化并建立连接，以及从微环境中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与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能分化并整合到成年动物或患有听神经病的动物的内耳中。未分化或部分分化的基质细胞将被移植到成年正常沙土鼠或经哇巴因治疗的沙土鼠的耳蜗内。在不同的实验条件下，对供体基质细胞的存活程度、神经元分化和轴突生长进行评估和比较。总之，这些实验将提供有关骨髓源干细胞在宿主耳蜗组织中分化和整合的关键因素的关键信息，从而对开发和实施听觉系统中的自体细胞替代疗法具有重要意义。

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.