Potential of Cord Blood Cells to Rescue Aging Brain

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），它们是老年人的疾病，导致显著的发病率和死亡率。 迄今为止，治疗这些疾病和正常衰老相关的学习和记忆下降的药理学方法已经取得了不同的成功，并且没有治疗可以阻止疾病的进展。用来自成人组织如人脐带血（人UCB或HUCB）的多能干细胞进行治疗性干预的潜力是有希望的，但尚未得到充分研究。 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。 在这项提案中，我们将研究HUCB细胞的发育潜力，使用移植到脑室下区（SVZ）的模型系统，并遵循细胞正常迁移路径的嗅球。 一个尚未回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个月、16个月和24个月大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性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细胞移植到各种老年大鼠宿主的SVZ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发生渐进性变化，因此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性改善。 为了解决这个问题，我们将用HUCB细胞处理老年大鼠，并跟踪它们在工作记忆测试（12臂桡臂水迷宫）中的表现。

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.