Minority predoctoral fellowship program

少数族裔博士前奖学金计划

• 批准号: 6450505
• 负责人: XILMA R ORTIZ-GONZALEZ
• 金额: $ 3.35万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6450505
• 关键词: Alzheimer's disease; acetylcholine; animal old age; behavior test; bone marrow; brain; cell differentiation; cell migration; disease /disorder model; gene delivery system; gene expression; gene therapy; histology; human tissue; infant animal; laboratory rat; memory; nerve growth factors; nervous system transplantation; neural degeneration; nonhuman therapy evaluation; predoctoral investigator; stem cell transplantation; stem cells; transfection

DESCRIPTION (provided by investigator): This proposal intends to explore the therapeutic potential of human bone marrow derived multipotent adult stem cells (MAPCs) for neural transplantation and repair. MAPCs could provide a (1) source of grafting tissue for cell replacement therapies and (2) gene therapy vehicles to correct metabolic or neurochemical deficiencies in the CNS. We will test whether human MAPCs can migrate and undergo neuronal, site-specific differentiation in vivo by transplanting them into neonatal rats. Since cholinergic basal forebrain degeneration is correlated with cognitive decline in Alzheimer?s disease, we will particularly addresss the potential for cholinergic differentiation of MAPCs when transplanted in this region. Ex-vivo nerve growth factor gene transfer has been shown to be a suitable approach to improve the cognitive deficits associated with degeneration of the basal forebrain cholinergic system, as seen in aging and Alzheimer?s disease. As gene therapy vehicles, we are interested in determining the effectiveness of NGF-secreting MAPCs transplants to ameliorate the cognitive deficits of animals with partial cholinergic immunolesions. Therefore, our experiments will test the role for MAPCs as a readily available source for neural transplantation tissue that besides the advantage of being amenable to expansion, differentiation and genetic manipulation in vitro, also embodies the unique prospect for autologous transplantation.

描述（调查员提供）：该提案打算探索 人骨髓的治疗潜力衍生多能的成年干细胞 （MAPC）用于神经移植和修复。 MAPC可以提供（1）源 用于细胞替代疗法的嫁接组织和（2）基因疗法 纠正中枢神经系统中的代谢或神经化学缺陷。我们将测试 人MAPC是否可以迁移和经历特定于现场的神经元 通过将它们移植到新生大鼠中，在体内分化。自从 胆碱能基础前脑变性与认知下降相关 在阿尔茨海默氏病中，我们将特别解决 在该区域移植时，MAPC的胆碱能分化。前体 神经生长因子基因转移已被证明是一种合适的方法 改善与基础变性有关的认知缺陷 前脑胆碱能系统，如衰老和阿尔茨海默氏病中所见。作为基因 治疗车辆，我们有兴趣确定 分泌NGF的MAPC移植以改善动物的认知缺陷 具有部分胆碱能免疫。因此，我们的实验将测试 MAPC作为随时可用的神经移植来源的作用 除了适合扩张的优势外， 分化和遗传操作在体外也体现了独特的 自体移植的前景。