The primary goal of this research is to obtain well defined, alternate sources of neural tissue for brain implantation to remedy central nervous system disorders such as Parkinson's disease. Three sources of neuronal cells will be examined and modulated in vitro to establish the potential of these cells for integration and stability within the host brain. (i) Established neuronal cell lines will be differentiated in vitro with antimitotic agents, vitamin A analogs and growth modulators and studied for cell surface properties and cell cycle kinetics. (ii) Dopaminergic neuronal cell hybrids will be produced by cell fusion of mitotic glial cells with embryonic substantia nigra cells to establish long- term, continuous, cultures of central dopamine neurons. These cells will also be screened for cell surface properties which are important criteria for potential integration within brain parenchyma. (iii) In addition, human and monkey adrenal medulla will be obtained from organ donation and cultured in vitro with growth factors and cocultured with cells which produce growth factors. Long-term cultures will be characterized for neuronal properties, the expression of transplantation antigens and colocalization of neuropeptides in this potentially transplantable tissue. Results of these studies will make available neural cells tailored for transplantation into primates with optimal characteristics and will lay the groundwork for repair of human CNS neurodegenerative diseases such as Parkinson's disease.
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