Physiology of Neurons from Human & Mouse ES Cells

人类神经元的生理学

• 批准号: 6688954
• 负责人: James E Huettner
• 金额: $ 29.07万
• 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/6688954
• 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）：本研究的目的是表征源自胚胎干（ES）细胞的神经元的体外和体内生理学特征。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细胞可以在体外分化成多种体细胞类型，包括神经元、星形胶质细胞和少突胶质细胞。此外，分化的 ES 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整合。基于小鼠 ES 细胞的这项工作，人类 ES 细胞的分离提高了新型替代疗法的可能性，其中体外分化的 ES 细胞将替代因损伤或疾病而损失的体细胞。可能适合替代疗法的神经系统病理包括帕金森病、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支持对现有人类胚胎干细胞系的研究，这引发了人们对探索干细胞衍生替代品作为解决这些以前棘手的缺陷的新方法的热情。然而，在实现这种疗法之前，仍有许多基础研究要做。 我们的最终目标是开发将人类 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优化 ES 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。目前，有关分化 ES 细胞生理学的信息有限。因此，该提案的目标是：1) 评估源自不同 ES 诱导方案的神经细胞的生理分化。 2) 表征 ES 衍生神经元移植到大脑后的生理学特征，包括对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 ES 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 细胞的研究都将使用 NIH 人类 ES 细胞登记处的 WA01 系。