Characterization of adult and embryonic stem cell proliferation, differentiation, and integration in vitro and in a nigrostriatal slice culture system

Stem cell therapy holds great promise in repairing brain damage caused by neurodegenerative diseases, such as Parkinson's disease. To fully use these cells, a better understanding is needed of the mechanisms and processes that control their proliferation, migration, and differentiation. Our study used both in vitro and slice culture techniques to examine adult neural and embryonic stem cells. Our initial experiments showed that adult neural stem cells can generate hybrid cells (asterons) in culture. These asterons appear to be hybrid cells that express both markers of immature neurons and astrocytes, and appear to be the result of transdifferentiation from a neuron to an astrocyte.; We also examined the effects of different extracellular matrix molecules on the migration of adult neurosphere derived cells. Our results showed that laminin and fibronectin are permissive for migration and enhance outgrowth. In contrast, chondroitin sulfate proteoglycan inhibits migration and impedes outgrowth.; Finally, to better assess stem cell integration into the central nervous system, we devised a novel slice-culture system that recreates the degeneration seen in Parkinson's disease. Using this slice culture model, we showed that ES cell-derived neurons can survive in culture, and integrate synaptically. We also were able to dopaminize these ES derived neurons and show that they maintain their dopamine phenotype in the slice. To enhance transplant integration, we examined the effect of adding extracellular matrix to the cell transplant. Our results suggest that laminin enhances the integration of these cells into the slice.; Our study examined the plasticity of adult and embryonic stem cells in culture and showed that these cells are responsive to environmental factors that interact with their differentiation and migration. Development of a slice culture model system that recreates the neuronal environment allows the development and future use of transplant enhancements for stem cell grafts into the brain.