Neuropathology in transplants in Parkinson's disease. Implications for disease pathogenesis and the future of cell therapy

Neural transplantation is over a century old, but the modern era encompasses only the last 30-40 years. For most of this time period, research has focused on reversing disability engendered by neurologic disease and brain damage. Only recently was it recognized that the underlying neurological disease itself might negatively impact the grafted neurons. We have found that a subset of neurons within embryonic neural grafts that survive more than 10 years in Parkinson patients display Lewy bodies, a classical feature of Parkinson's disease neuropathology. Additionally, the grafted cells placed in the Parkinson's disease brain eventually downregulate the expression of dopamine transporter and tyrosine hydroxylase in a manner similar to what is seen in the substantia nigra dopamine neurons that are degenerating due to the disease. We discuss these findings in terms of how they might improve our understanding of Parkinson's disease pathogenesis and the effects they may have on the future of neural cell replacement strategies.