Physiology of Neurons from Human & Mouse ES Cells

人类神经元的生理学

• 批准号: 6984071
• 负责人: James E Huettner
• 金额: $ 28.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984071
• 关键词: Physiology; Neurons; Human; Mouse; ES

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：这项研究的目的是表征源自胚胎茎（ES）细胞的神经元的体外和体内生理学。这些细胞代表了用于研究和治疗的多能，遗传正常细胞的潜在无限来源。小鼠ES细胞可以在体外区分各种体细胞类型，包括神经元，星形胶质细胞和少突胶质细胞。此外，分化的ES细胞在移植到大脑或脊髓后生存并与周围宿主组织的形态整合。基于小鼠ES细胞的这项工作，人类ES细胞的分离增加了新型替代疗法的可能性，在这种替代疗法中，体外分化的ES细胞将代替损失损伤或疾病的体细胞。神经系统的病理学可能可以接受替代疗法，包括帕金森氏病，疗法横向硬化症，中风，亨廷顿氏病和多发性硬化症。布什总统决定允许联邦对现有人类ES线路研究的支持，这引起了人们极大的热情探索干细胞衍生的替代者的希望，以此作为解决这些以前棘手的赤字的一种新方法。但是，在实现此类疗法之前，还有许多基础研究要做。 我们的最终目标是开发将人ES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中时将ES衍生神经元的整合到功能网络中。功能整合的一个重要组成部分是从单个干细胞得出的神经元获得正常生理特性。在这一点上，只有有关分化ES细胞生理的有限信息。因此，该提案的目标是：1）评估来自不同ES诱导方案的神经细胞的生理分化。 2）将移植到大脑后的ES衍生神经元的生理学表征，包括对与周围宿主神经元的功能突触连接形成的严格测试。人和小鼠ES细胞将并行使用它们的发育潜力。所有对人ES细胞的研究将在NIH人ES细胞注册表中使用WA01系。