Potential of Cord Blood Cells to Rescue Aging Brain

脐带血细胞拯救衰老大脑的潜力

• 批准号: 6890359
• 负责人: ALISON E WILLING
• 金额: $ 25.38万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 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 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6890359
• 关键词: Alzheimer' s disease; Parkinson' s disease; age difference; aging; animal old age; behavior test; biological models; cell differentiation; cell migration; cerebral ventricles; cord blood; growth factor; hippocampus; human subject; immunocytochemistry; laboratory rat; learning; mature animal; memory; neural degeneration; neurotrophic factors; nonhuman therapy evaluation; psychological aspect of aging; stem cell transplantation; tissue /cell culture

The normal aging process leads to a variety of changes in the central nervous system that underlie alterations in learning and memory as well as balance coordination. In addition, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), which are diseases of the aged, lead to significant morbidity and mortality. To date the pharmacological approaches to treatments of these diseases and normal aging related declines in learning and memory have been of varying success and no treatment stops the disease progression. The potential for therapeutic intervention with multipotent stem cells from adult tissues such as human umbilical cord blood (human UCB or HUCB) holds promise, yet has not been fully examined. We have chosen HUCB as it is a rich source of immature progenitor cells and is readily available. In this proposal we will study the developmental potential of HUCB cells using a well characterized model system of transplantation into the subventricular zone (SVZ) and following the cells normal migratory path to the olfactory bulb. One question that remains unanswered is how the age of the recipient alters the capacity of HUCB progenitors to develop into appropriate neural cell types. We will examine this by transplanting HUCB progenitors into rats of 6, 16, and 24 months of age and follow the fate of the transplanted HUCB cells. A second critical question is whether exogenous growth and neurotrophic factors will increase the differentiation of HUCB cells into distinct neural phenotypes and if these neuralized HUCB cells will be more (or less) successful when transplanted into the SVZ of various aged rat hosts. Finally, as there are progressive changes in learning and memory with age a critical area to examine is whether HUCB therapy can produce a functional improvement on learning and memory tasks in the aged rats. To address this question we will treat aged rats with HUCB cells and follow their performance on a test of working memory, the 12 arm radial arm water maze.

正常的衰老过程导致中枢神经系统的各种变化，这些变化是学习和记忆以及平衡协调的改变。 此外，神经退行性疾病，例如阿尔茨海默氏病（AD）和帕金森氏病（PD），这些疾病是老年人的疾病，导致了显着的发病率和死亡率。 迄今为止，这些疾病治疗的药理学方法和在学习和记忆方面的正常衰老相关下降的成功已经有所不同，没有治疗可以阻止疾病的进展。从成年组织（如人UCB或HUCB）中与多能干细胞进行治疗干预的潜力是有望的，但尚未得到充分检查。 我们选择了HUCB，因为它是不成熟祖细胞的丰富来源，并且很容易获得。 在该提案中，我们将使用良好表征的移植到室室下区（SVZ）的模型系统研究HUCB细胞的发育潜力，并遵循细胞正常迁移到嗅球的迁移路径。 尚未解决的一个问题是，受体的年龄如何改变HUCB祖细胞发展为适当的神经细胞类型的能力。我们将通过将HUCB祖细胞移植到6、16和24个月大的大鼠中，并遵循移植的HUCB细胞的命运来研究这一点。 第二个关键问题是，外源生长和神经营养因素是否会增加HUCB细胞为不同的神经表型的分化，以及当移植到各种老鼠宿主的SVZ中时，这些神经化的HUCB细胞是否会更成功（或更少）。最后，随着年龄的学习和记忆的逐渐变化，需要检查的关键领域是HUCB治疗是否可以对老年大鼠的学习和记忆任务产生功能改善。 为了解决这个问题，我们将使用HUCB细胞处理老年大鼠，并在工作记忆测试中进行12臂径向臂水迷宫的表现。