Potential of Cord Blood Cells to Rescue Aging Brain

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、记忆和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），这是老年人的疾病，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衰退的药理学方法取得了不同程度的成功，没有任何治疗可以阻止疾病的进展。利用成人组织（如人脐带血）的多能干细胞（human UCB或HUCB）进行治疗干预的潜力充满希望，但尚未得到充分研究。我们之所以选择hub，是因为它是未成熟祖细胞的丰富来源，而且很容易获得。在这一建议中，我们将研究hub细胞的发育潜力，使用一个很好的移植到心室下区（SVZ）的模型系统，并遵循细胞正常迁移到嗅球的路径。一个尚未解决的问题是，受体的年龄如何改变hub祖细胞发育成适当神经细胞类型的能力。我们将通过将hub祖细胞移植到6个月、16个月和24个月大的大鼠中并跟踪移植的hub细胞的命运来检验这一点。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hub细胞向不同神经表型的分化，以及这些神经化的hub细胞在移植到不同年龄大鼠宿主的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进行性变化，一个关键的研究领域是hub治疗是否能在老年大鼠的学习和记忆任务中产生功能改善。为了解决这个问题，我们将用hub细胞治疗老年大鼠，并跟踪它们在工作记忆测试中的表现，12臂径向臂水迷宫。

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.