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.

正常的衰老过程会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能力变化的基础。此外，神经退行性疾病，如阿尔茨海默病(AD)和帕金森病(PD)，是老年人的疾病，导致显著的发病率和死亡率。到目前为止，治疗这些疾病和正常衰老相关的学习和记忆下降的药物方法取得了不同程度的成功，没有任何治疗方法可以阻止疾病的发展。利用成人组织中的多能干细胞(如人脐血或人脐血)进行治疗干预的潜力很有希望，但尚未得到充分检验。我们选择了HUCB，因为它是一个丰富的未成熟祖细胞来源，而且很容易获得。在这项建议中，我们将使用一个具有良好特性的移植到脑室下区(SVZ)的模型系统来研究HUCB细胞的发育潜力，并遵循细胞向嗅球的正常迁移路径。一个悬而未决的问题是，受者的年龄如何改变人脐血祖细胞发育为适当神经细胞类型的能力。我们将通过将人脐血祖细胞移植到6个月、16个月和24个月大的大鼠体内来检验这一点，并跟踪观察移植的人脐血细胞的命运。第二个关键问题是外源性生长和神经营养因子是否会增加HUCB细胞向不同神经表型的分化，以及这些神经化的HUCB细胞移植到不同老年大鼠的SVZ是否会更成功(或更不成功)。最后，由于学习和记忆随着年龄的增长而逐渐改变，因此需要研究的一个关键领域是HUCB治疗是否能够改善老年大鼠的学习和记忆任务。为了解决这个问题，我们将用HUCB细胞治疗衰老的大鼠，并观察它们在工作记忆测试中的表现，即12臂放射状手臂水迷宫。