Minority predoctoral fellowship program

少数族裔博士前奖学金计划

• 批准号: 6896129
• 负责人: XILMA R ORTIZ-GONZALEZ
• 金额: $ 3.61万
• 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 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6896129
• 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（由研究者提供）：本提案旨在探索 人骨髓来源的多能成体干细胞的治疗潜力 （MAPC）用于神经移植和修复。 MAPC 可以提供 (1) 来源 用于细胞替代疗法的移植组织和（2）基因治疗载体 纠正中枢神经系统的代谢或神经化学缺陷。我们将测试 人类 MAPC 是否可以迁移并经历神经元、位点特异性 通过将它们移植到新生大鼠体内进行体内分化。自从 胆碱能基底前脑变性与认知能力下降相关 在阿尔茨海默氏病中，我们将特别关注 MAPCs 移植到该区域后会发生胆碱能分化。离体 神经生长因子基因转移已被证明是一种合适的方法 改善与基底退化相关的认知缺陷 前脑胆碱能系统，如衰老和阿尔茨海默病中所见。作为基因 治疗工具，我们有兴趣确定其有效性 分泌 NGF 的 MAPC 移植可改善动物的认知缺陷 伴有部分胆碱能免疫损伤。因此，我们的实验将测试 MAPC 作为神经移植的现成来源的作用 组织除了易于扩张的优点之外， 体外分化和基因操作，也体现了独特的 自体移植的前景。