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.
