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Development and Utilization of Dopaminergic Cell Lines for the Treatment of Parkinson's Disease

We have recently succeeded in differentiating adult human and animal bone marrow stromal stem cells (BMSCs) into neurons (nerve cells). A subpopulation of the neurons activates functions that are characteristic of the nerves that degenerate in Parkinson's disease. We are now isolating, expanding, and further differentiating the neurons for use in Parkinson's disease. Use of BMSCs for transplantation confers a number of potential therapeutic advantages. Transplantation of the patient's own cells eliminates the hazards of immunorejection and the need for toxic immunosuppressive agents. The bone marrow is a safe, accessible source, and provides a renewable population of cells. BMSCs grow rapidly, eliminating the need for development of a tumor line (immortalization), and they differentiate into neurons using simple methods. Finally, the use of adult cells circumvents the concerns attendant to the use of embryonic tissue. We are now defining these neurons in greater detail to determine whether they synthesize and send the chemical signal that is deficient in Parkinson's disease. Based on these studies, we will maximize utility for Parkinson's disease by growing the BMSCs or neurons under different conditions and by inserting genes to enhance function. The adult bone marrow cells are particularly advantageous since they divide rapidly, are extremely flexible, and accept new genes without difficulty. We have already transplanted the differentiated neurons to various regions of animal brains, including those affected in Parkinson's disease, and the cells survive for at least one and a half months-the longest time examined. Utility of the BMSCs and neurons will be tested in animal models of Parkinson's disease. Successful approaches will be applied to human cells from the animal prototypes. Our overall goal is to develop human lines for use in Parkinson's disease.


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