Physiology of Neurons from Human & Mouse ES Cells

本研究的目的是研究体外和体内分化的神经元的生理学特征。 来自胚胎干细胞。从基因上讲，这些细胞代表着潜在的无限多能来源。 用于研究和治疗的正常细胞。小鼠胚胎干细胞在体外可分化为多种体细胞 类型包括神经元、星形胶质细胞和少突胶质细胞。此外，分化后的ES细胞存活并 移植到脑内后，在形态上与周围宿主组织整合 脊髓。基于对小鼠ES细胞的这项工作，人类ES细胞的分离提高了 体外分化的ES细胞将替代体细胞的新替代疗法的可能性 细胞因损伤或疾病而丢失。神经系统的病变，可能是可以替换的 治疗包括帕金森氏症、肌萎缩侧索硬化症、中风、亨廷顿病和多发性 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的研究， 引发了极大的热情，探索干细胞来源的替代作为一种新的方式的前景 解决这些以前难以解决的缺陷；然而，在此之前，仍有许多基础研究要做 治疗是可以实现的。 我们的最终目标是开发有效地将人类胚胎干细胞转化为特定类型的程序 并在移植时优化胚胎干细胞来源的神经元与功能网络的整合 进入宿主神经系统。功能集成的一个重要组成部分是获得正常的 单个干细胞来源的神经元的生理特性。在这一点上，只有有限的信息是 可获得有关分化的ES细胞的生理学知识。因此，这项提议的目标是： 1)评价不同ES诱导方案来源的神经细胞的生理分化。 2)研究胚胎干细胞来源的神经元移植到脑内后的生理学特征，包括 与周围宿主神经元形成功能性突触连接的严格测试。人与人 小鼠胚胎干细胞将被并行使用，以比较它们的发育潜力。所有关于人类ES的研究 细胞将使用NIH人类ES细胞注册表中的WA01系。

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.