Physiology of Neurons from Human & Mouse ES Cells

超出所提供的空间。本研究的目的是表征胚胎干细胞（ES）神经元的体外和体内生理特征。这些细胞为研究和治疗提供了潜在的无限多能、基因正常的细胞来源。小鼠胚胎干细胞可以在体外分化为多种体细胞类型，包括神经元、星形胶质细胞和少突胶质细胞。此外，分化的胚胎干细胞在移植到大脑或脊髓后能够存活，并在形态上与周围宿主组织结合。在小鼠胚胎干细胞的研究基础上，人类胚胎干细胞的分离提出了一种新的替代疗法的可能性，在这种疗法中，体外分化的胚胎干细胞将取代因损伤或疾病而丧失的体细胞。可能适用于替代疗法的神经系统病理包括帕金森病、肌萎缩性侧索硬化症、中风、亨廷顿氏病和多发性硬化症。布什总统决定允许联邦政府支持对现有人类胚胎干细胞系的研究，这引起了人们对探索干细胞衍生替代品的希望的极大热情，作为解决这些先前难以解决的缺陷的新方法；然而，在实现这种疗法之前，还有许多基础研究要做。我们的最终目标是开发将人类胚胎干细胞有效转化为特定类型神经元的程序，并在移植到宿主神经系统时优化胚胎干细胞衍生神经元与功能网络的整合。功能整合的一个重要组成部分是个体干细胞衍生的神经元获得正常的生理特性。在这一点上，只有有限的信息是可用的生理学分化胚胎干细胞。因此，本研究的目的是：1)评估不同ES诱导方案下神经细胞的生理分化。2)表征es来源神经元移植入脑后的生理特征，包括与周围宿主神经元形成功能性突触连接的严格测试。人类和小鼠胚胎干细胞将同时使用，以比较它们的发育潜力。所有关于人类胚胎干细胞的研究都将使用美国国立卫生研究院人类胚胎干细胞登记处的WA01系。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The objective of this research is to characterize the in vitro and in vivo physiology of neurons derived from embryonic stem (ES) cells. These cells represent a potentially limitless source of pluripotent, genetically normal cells for research and therapy. Mouse ES cells can differentiate in vitro into a variety of somatic cell types including neurons, astrocytes and oligodendrocytes. In addition, differentiated ES cells survive and become morphologically integrated with surrounding host tissue following transplantation into the brain or spinal cord. Based on this work with mouse ES cells, the isolation of human ES cells has raised the possibility for novel replacement therapies in which in vitro differentiated ES cells will substitute for somatic cells lost to injury or disease. Pathologies of the nervous system that might be amenable to replacement therapy include Parkinson's disease, amyotophic lateral sclerosis, stroke, Huntington's disease, and multiple sclerosis. President Bush's decision to allow federal support for research on existing human ES lines has engendered great enthusiasm to explore the promise of stem cell-derived replacement as a new way to address these previously intractable deficits; however, much basic research remains to be done before such therapies can be achieved. Our ultimate goals are to develop procedures for efficient conversion of human ES cells into specific types of neurons and to optimize the integration of ES-derived neurons into functional networks when transplanted into a host nervous system. An essential component of functional integration is the acquisition of normal physiological properties by individual stem cell derived neurons. At this point, only limited information is available about the physiology of differentiated ES cells. Thus, the goals of this proposal are: 1) To evaluate physiological differentiation of nerve cells derived from distinct ES induction protocols. 2) To characterize the physiology of ES-derived neurons after transplantation into the brain, including rigorous tests for formation of functional synaptic connections with surrounding host neurons. Human and mouse ES cells will be used in parallel to compare their developmental potentials. All research on human ES cells will use the WA01 line in the NIH human ES cell registry. PERFORMANCE SITE ========================================Section End===========================================