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: 6629382
• 负责人: Tanja Zigova
• 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/6629382
• 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发生各种变化，从而导致学习和记忆以及平衡协调能力的改变。 此外，神经退行性疾病，例如阿尔茨海默病（AD）和帕金森病（PD），这些老年疾病，导致显着的发病率和死亡率。 迄今为止，治疗这些疾病和正常衰老相关的学习和记忆力下降的药理学方法已取得了不同程度的成功，并且没有任何治疗可以阻止疾病的进展。利用来自成人组织（例如人脐带血（人 UCB 或 HUCB））的多能干细胞进行治疗干预的潜力有希望，但尚未得到充分检验。 我们选择 HUCB 是因为它是未成熟祖细胞的丰富来源并且容易获得。 在本提案中，我们将使用特征明确的模型系统移植到室下区（SVZ）并遵循细胞正常迁移路径到嗅球，研究 HUCB 细胞的发育潜力。 一个尚未解答的问题是受体的年龄如何改变 HUCB 祖细胞发育成适当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 个月龄的大鼠中来检查这一点，并跟踪移植的 HUCB 细胞的命运。 第二个关键问题是外源生长和神经营养因子是否会增加 HUCB 细胞分化为不同的神经表型，以及这些神经化的 HUCB 细胞在移植到各种老年大鼠宿主的 SVZ 中时是否会更成功（或更不成功）。最后，由于学习和记忆随着年龄的增长而逐渐发生变化，需要检查的一个关键领域是 HUCB 治疗是否可以对老年大鼠的学习和记忆任务产生功能性改善。 为了解决这个问题，我们将用 HUCB 细胞治疗老年大鼠，并跟踪它们在工作记忆测试（12 臂径向臂水迷宫）中的表现。