La Jolla Interdisciplinary Neuroscience Center Cores - Stem Cell Core BU

拉荷亚跨学科神经科学中心核心 - 干细胞核心事业部

• 批准号: 8132843
• 负责人: STUART A LIPTON
• 金额: $ 6.36万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8132843
• 关键词: Adult; Animals; Applications Grants; Area; Astrocytes; Behavior; Bioinformatics; Biological Assay; Biology; Brain; California; Cannulations; Catheterization; Cell Line; Cell Therapy; Cells; Cellular biology; Characteristics; Clinical; Clone Cells; Cluster Analysis; Collaborations; Communication; Communities; Complex; Computer software; Consultations; Core Facility; Cryopreservation; Custom; Data; Data Analyses; Databases; Derivation procedure; Detection; Development; Differentiation Antigens; ES Cell Line; Embryo; Ensure; Environment; Equipment; Ethics; Evaluation; Event; Experimental Designs; Faculty; Flow Cytometry; Fostering; Funding; Future; Gene Duplication; Gene Expression; Generations; Genes; Genome; Goals; Grant; Guidelines; Human; Human Resources; Image; Image Analysis; Immunohistochemistry; In Vitro; Injection of therapeutic agent; Institutes; International; Intravenous; Karyotype determination procedure; Knowledge; Laboratories; Lead; Link; Manuscripts; Measures; Medical Research; Mentors; Methods; Microarray Analysis; Microscopy; Motor Neurons; Mus; Muscle Fibers; Neurons; Neurosciences; Newborn Infant; Northern Blotting; Outcome; Output; Pathway Analysis; Play; Population; Preparation; Procedures; Proteins; Proteome; Proteomics; Protocols documentation; Publishing; Quality Control; RNA; Rattus; Regenerative Medicine; Reporter; Reporting; Research; Research Personnel; Research Project Grants; Resources; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; SNP genotyping; Sampling; Savings; Scanning; Scientist; Senile Plaques; Services; Sorting - Cell Movement; Spinal Cord; Staging; Standardization; Stem Cell Research; Stem cell transplant; Stem cells; Supervision; Techniques; Technology; Time; Training; Training Support; Transplantation; Ultrasonography; United States National Institutes of Health; Work; Writing; adult stem cell; cell type; clinical application; cost; design; embryonic stem cell; experience; fetal; gene therapy; genetic manipulation; genome-wide; human embryonic stem cell; human embryonic stem cell line; improved; in utero transplantation; insight; interdisciplinary collaboration; interest; meetings; member; monolayer; nerve stem cell; nervous system disorder; neurogenesis; neuron development; novel; novel strategies; promoter; protein expression; research facility; research study; self-renewal; skills; stem; stem cell differentiation; tool; transgenic model of alzheimer disease; user-friendly

STEM CELL CORE 1. MAIN OBJECTIVES AND NEW DIRECTIONS The Stem Cell Core will be a new facility. Currently, there is no unified Stem Cell Core Facility to link neuroscientists on the La Jolla Torrey Pines Mesa. Therefore, this Stem Cell facility will constitute a new Core to foster stem cell projects and collaborations among neuroscientists in the San Diego area. Interest in human embryonic stem cells (hESCs) has grown steadily since the report of the first hESC line in 1998. hESCs are attractive because of their potential as cell therapy, either directly replacing cells or by using them as vehicles for gene therapy (Muller et al. 2006). But the cells themselves are intrinsically interesting, because of their unique qualities of pluripotence and self-renewal, and these qualities have led to a resurgence of interest in fundamental cell biology. hESC are the perfect tools to study events that occur during human neurogenesis, both to understand normal development and to identify what goes wrong during neurological disease. The versatility of hESC means that from the same population one can generate multiple cell types that can then be used to dissect complex cellcell interactions. For example, by differentiating hES cells into motor neurons, skeletal muscle cells, and astroglia, one can do mix-and-match experiments to identify the vital components of degeneration in ALS. By generating human/mouse chimeric brains using transplanted human neural stem cells or neuronal precursors derived from hESC, it will be possible to ask how human neurons react to the amyloid plaques that develop in transgenic models of Alzheimer's disease. Additionally, hESCs will eventually be used for transplantation therapies in regenerative medicine. This Core facility proposes to use only approved Presidential ES cell lines. The funds requested are particularly important because Prop 71 which was to fund stem cell work in California has not become a reality, and it is currently not clear if these funds will become available in the future. In addition to hESCs, this core will allow neuroscientists on the La Jolla Torrey Pines Mesa access to methods regarding the use of murine (m)ES cells. Additionally, the Stem Cell Core has expertise with neural progenitor cells (NPCs) derived both from hES and mES cells. Moreover, NPCs from fetal human and mouse brains (obtained by workers at BIMR and UCSD), and adult rodent NPCs (from the laboratory of Fred Gage at The Salk Institute) will be available through this Stem Cell Core. The origins of all of these cells and cell lines have received both Institutional approval and Presidential approval, where necessary for hESC lines. The purpose of the Stem Cell Core will be to provide training and fundamental analysis tools for stem cell research throughout the La Jolla Torrey Pines Mesa. Currently, while there is an NIH-sponsored Stem Cell Center at the Burnham Institute for Medical Research (BIMR), it is aimed at specific projects and is insufficient to provide support for local neuroscientists who would like to use it. With this grant, we propose to take advantage of the BIMR's experienced Stem Cell Center faculty and staff and expand the capacity of the core laboratory to make the facilities available to all neuroscientists in the La Jolla Torrey Pines Mesa area (UCSD, Salk, BIMR and TSRI). The Stem Cell Core will be directed by Dr. Alexey Terskikh (BIMR, who trained with Prof. Irving Weismann, a well-known stem cell expert at Stanford. Co-directors of the facility will be stem cell experts Drs. Evan Snyder and Jeanne Loring (at BIMR), and Fred (Rusty) Gage and Juan Carlos Belmonte at The Salk Institute. The overall objective of the Stem Cell core is to lower the barrier for neuroscientists to involve stem cells in their research projects, by providing training and expert advice from experienced stem cell biologists. This will improve communication among scientists in a variety of neuroscience subspecialties to foster interdisciplinary collaborations and novel approaches. By sharing common techniques and accumulated knowledge about the fundamental biology of human ES cells and somatic (adult) stem cells, there will be a considerable savings in time, effort, and cost. The Stem Cell Core will play an important role in ensuring that the users are kept up to date with the standardization of hESC methods called for by the international stem cell scientific community (Andrews et al. 2005; Loring 2005). The principal focus of this core is to provide stem cell-specific technologies that will lead to new insights in neuroscience and aid in development of clinical applications for stem cells. For example, correlation of the characteristics of stem cells in culture and their behavior after transplantation will help in decisions about which cells to use and what quality control measures will be necessary for clinical use. Core support will include culturing of ES and other stem cells, karyotyping, SNP genotyping, microarray analysis, immunohistochemistry for stem cell and differentiation markers, assays for pluripotence and differentiation, and access to BIMR's extensive databases of stem cell information. In addition, the stem cell core faculty will offer advice for experimental design, data analysis, interpretation of results, and assistance with manuscripts and grant applications. Stem cell core faculty will also serve as mentors for postdocs and young faculty members, to help them publish and obtain grant support.

干细胞芯 1。主要目标和新方向 干细胞芯将是一个新的设施。目前，没有统一的干细胞核心设施可以链接 La Jolla Torrey Pines Mesa上的神经科学家。因此，该干细胞设施将构成 在圣地亚哥地区促进干细胞项目和神经科学家之间的合作的新核心。 自第一个hESC报告以来，对人类胚胎干细胞（HESC）的兴趣稳步增长 1998年的生产线。hESC由于其潜力作为细胞疗法而具有吸引力，要么直接替代 细胞或将它们用作基因治疗的车辆（Muller等，2006）。但是细胞本身是 本质上有趣的是，由于它们具有独特的多能和自我更新的特质，这些 品质导致对基本细胞生物学的兴趣复兴。 hESC是完美的工具 研究人类神经发生过程中发生的事件，既了解正常发育又 确定神经疾病期间出了什么问题。 hESC的多功能性意味着从 相同的人群可以生成多种细胞类型，然后可以用来剖析复杂的细胞细胞 互动。例如，通过将HES细胞区分为运动神经元，骨骼肌细胞， 和Astroglia，可以进行混合和匹配实验以识别变性的重要组成部分 在ALS中。通过使用移植的人类神经干细胞或 源自hESC的神经元前体，可以询问人类神经元如何反应 在阿尔茨海默氏病的转基因模型中发展的淀粉样斑块。此外，hESC会 最终用于再生医学中的移植疗法。这个核心设施提出了 仅使用批准的总统ES细胞系。要求的资金特别重要，因为 为加利福尼亚的干细胞工作提供资金的Prop 71尚未成为现实，目前是 尚不清楚这些资金是否会在将来可用。除了hESC，此核心还将 允许在La Jolla Torrey Pines Mesa访问有关使用鼠的方法的神经科学家 （M）ES细胞。此外，干细胞核具有神经祖细胞（NPC）的专业知识 均来自HES和MES细胞。此外，来自胎儿人和小鼠大脑的NPC（获得 由BIMR和UCSD的工人和成年啮齿动物NPC（来自Fred Gage实验室 Salk Institute）将通过此干细胞核心提供。所有这些细胞的起源和 在必要的必要时 hESC线。 干细胞核心的目的是为STEM提供培训和基本分析工具 整个La Jolla Torrey Pines Mesa的细胞研究。目前，虽然有一个NIH赞助的 伯纳姆医学研究所（BIMR）的干细胞中心，针对特定项目 而且不足以为希望使用它的本地神经科学家提供支持。与此 格兰特，我们建议利用BIMR经验丰富的干细胞中心教职员工 并扩大核心实验室的能力，使所有神经科学家都可以使用这些设施 La Jolla Torrey Pines Mesa地区（UCSD，Salk，Bimr和TSRI）。干细胞芯将被定向 由Alexey Terskikh博士（BIMR，他曾与著名的干细胞Irving Weismann教授培训 斯坦福大学的专家。该设施的联合导演将是干细胞专家DRS。埃文·斯奈德和珍妮 Loring（在BIMR）以及Salk Institute的Fred（Rusty）Gage和Juan Carlos Belmonte。 干细胞核的总体目标是降低神经科学家涉及茎的障碍 通过提供经验丰富的干细胞生物学家的培训和专家建议，其研究项目中的细胞。 这将改善科学家在各种神经科学亚专业中的沟通 促进跨学科的合作和新颖的方法。通过共享通用技术和 关于人ES细胞和体细胞（成人）茎的基本生物学的积累知识 细胞，时间，精力和成本将有大量节省。干细胞芯将发挥重要作用 在确保用户与hESC方法的标准化保持最新状态方面 由国际干细胞科学界要求（Andrews等，2005； Loring 2005）。 该核心的主要重点是提供特定于干细胞的技术，这些技术将带来新的见解 在神经科学和有助于开发干细胞的临床应用中。例如， 干细胞在培养和移植后其行为的特征的相关性将 帮助决定要使用哪些单元格以及需要采取哪些质量控制措施 临床用途。核心支持将包括培养ES和其他干细胞，核分型，SNP基因分型， 微阵列分析，干细胞和分化标记的免疫组织化学，测定 多功能和分化，以及访问BIMR的干细胞信息广泛数据库。 此外，干细胞核心教师将为实验设计，数据分析，解释提供建议 结果，以及手稿和赠款申请的协助。干细胞核心教师将 还为博士后和年轻教师担任导师，以帮助他们出版和获得赠款 支持。