Cytokine Induction of Dopamine Neurons from Progenitor Cells

摘要

Significant progress has been made on all aspects of the originally described work and the project is proceeding as planned and is ahead of schedule. The mesencephalic progenitor cells have been successfully cloned, characterized and shown to share numerous phenotypic characteristics with primary mesencephalic cells. We have also shown that the clones can be cryopreserved. In addition, the cloned and converted cells respond to traditional DA neurotoxins possess Nurr1 like normal primary DA neurons. We have developed assays for calbindin and microglia that will be applied to the clones. In addition, we have successfully grafted the cloned cells in the striatum of rats with 6-hydroxydopamine lesions and demonstrated proof of principle.. i.e., progenitor cells converted to DA neurons by hematpoietic cytokines can attenuate behavioral asymmetries and survive as DA neurons in a fashion similar to that seen when primary mesencephalon is used. This later experiment was the primary focus of the original proposal. Finally, as a result of the knowledge gained through our work with cytokines in DA neuron development, we have expanded our studies into the role cytokines play in DA neuron degeneration with the intention of demonstrating that pro-inflammatory cytokines are a risk factor for Parkinson's disease.