In Vivo Control and Functional Visualization of Stem Cell-Driven CNS Regeneration

干细胞驱动的中枢神经系统再生的体内控制和功能可视化

• 批准号: 7981828
• 负责人: Jin Hyung Lee
• 金额: $ 15.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981828
• 关键词: Address; Alzheimer' s Disease; Cells; Central Nervous System Diseases; Complex; Development; Functional Magnetic Resonance Imaging; Genetic; Genetic Techniques; Imagery; Imaging Techniques; Interphase Cell; Maps; Multiple Sclerosis; Natural regeneration; Nature; Nerve Regeneration; Nerve Tissue; Neuraxis; Neurons; Parkinson Disease; Process; Reporting; Resolution; Spinal cord injury; Stem cell transplant; Stem cells; Stroke; Techniques; Textiles; Transfection; Viral Vector; abstracting; base; cell type; in vivo; in vivo regeneration; induced pluripotent stem cell; innovation; neural circuit; neurogenesis; novel; relating to nervous system; stem cell biology; stem cell therapy; success; therapeutic development

DESCRIPTION (Provided by the applicant) Abstract: This proposal suggests a consilience of bold new concepts in genetics, stem cell biology, and functional magnetic resonance imaging (fMRI) to address a singular question that could never be tapped previously: can we directly map the functionality of stem cell-driven neural circuit regeneration in vivo? Despite the debilitating character of central nervous system (CNS) diseases, and the urgency for therapeutic development, the complex nature of the neural fabric underlying CNS diseases such as spinal cord injuries, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and stroke, substantially negate their viable cure to date. Here, the fundamental ability of stem cells to regenerate non-dividing cells, as well as recent development of induced pluripotent stem cells (IPSC) gives fresh impetus for a whole new class of innovative treatments where damaged neural circuitry might be partially or fully restored by stem-cell induced neurogenesis. We seek to be instrumental in this pivotal endeavor by introducing a completely novel way of directly assessing the functionality of stem cell driven neural circuitry in vivo. This will be achieved by combining genetic techniques that will introduce modulatory and/or reporting capability to neural cells based on its cell type. We will strategically introduce viral vectors to both the underlying neural circuit as well as transplanted stem cells. For stem cell transfection, we expect our proposed technique to allow modulatory/reporting capability from only those developing into specific cell types. This cell-specific modulation/reporting capability will then combined with a novel distortion-free fMRI imaging technique, permitting non-invasive and high-resolution visualization of the regeneration processes. This project, upon its success, will provide direct functional assessment capabilities for the regenerated nerve tissue in vivo. This in turn will provide key guidance for developing novel stem cell therapies for CNS diseases. Public Health Relevance: The complexity and functional nature of neural circuitry makes central nervous systems (CNS) diseases such as spinal cord injuries, Parkinson's disease, Alzheimer's disease, multiple sclerosis, and stroke particularly challenging for therapeutic approaches. While recent development of induced pluripotent stem cells (IPSC) gives fresh impetus for a whole new class of innovative treatment landscapes for patients with debilitating CNS diseases, the ultimate functionality of stem cell induced CNS regeneration remains elusive. This project, upon its success, will provide direct and functional assessment capabilities for the regenerated nerve tissue in vivo. This in turn will provide key guidance for developing novel stem cell therapies for CNS diseases.

描述（由申请人提供） 摘要：这项提议表明了遗传学，干细胞生物学和功能性磁共振成像（fMRI）中大胆的新概念的一致性，以解决以前从未开发过的单一问题：我们能否直接映射干细胞驱动的神经回路再生的功能？尽管中枢神经系统（CNS）疾病的衰弱特征和治疗开发的紧迫性，但CNS疾病如脊髓损伤、帕金森病、阿尔茨海默病、多发性硬化和中风的神经结构的复杂性质基本上否定了它们迄今为止的可行治愈。在这里，干细胞再生非分裂细胞的基本能力，以及诱导多能干细胞（IPSC）的最新发展为一类全新的创新治疗提供了新的动力，其中受损的神经回路可能通过干细胞诱导的神经发生部分或完全恢复。我们试图通过引入一种全新的方法来直接评估干细胞驱动的体内神经回路的功能，从而在这一关键奋进中发挥作用。这将通过结合遗传技术来实现，该遗传技术将基于其细胞类型向神经细胞引入调节和/或报告能力。我们将战略性地将病毒载体引入潜在的神经回路以及移植的干细胞。对于干细胞转染，我们期望我们提出的技术允许仅来自那些发展成特定细胞类型的细胞的调节/报告能力。这种细胞特异性调制/报告能力将与一种新的无失真功能磁共振成像技术相结合，允许非侵入性和高分辨率的再生过程的可视化。该项目一旦成功，将为体内再生神经组织提供直接的功能评估能力。这反过来将为开发用于CNS疾病的新型干细胞疗法提供关键指导。 公共卫生相关性：神经回路的复杂性和功能性质使得中枢神经系统（CNS）疾病如脊髓损伤、帕金森病、阿尔茨海默病、多发性硬化和中风对于治疗方法而言特别具有挑战性。虽然诱导多能干细胞（IPSC）的最新发展为患有衰弱性CNS疾病的患者的全新一类创新治疗景观提供了新的动力，但干细胞诱导CNS再生的最终功能仍然难以捉摸。该项目一旦成功，将为体内再生神经组织提供直接和功能评估能力。这反过来将为开发用于CNS疾病的新型干细胞疗法提供关键指导。