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The transplantation of human fetal ventral mesencephalic (VM) tissue for patients with advanced Parkinson's disease (PD) has now proved to be of benefit in early clinical trials (1-3). This has been clearly seen in terms of improved motor function, which has been correlated with increased fluorodopa signal on positron emission tomographic scanning at the site of the implant and the presence of abundant tyrosine hydroxylase (TH)-positive neurons in those patients who have come to postmortem analysis (4,5). However, although the concept of restoration of function through neural transplantation is promising, there are major practical as well as ethical problems with the use of aborted human fetal tissue. In particular, aborted fetal tissue is not available in many countries, and even where it can be obtained, isolation of the VM from the large numbers of fetuses the procedure requires presents major logistical difficulties. For example, in PD the best results have been obtained using an average of six to eight fetuses per patient. Therefore, the search for alternative sources of tissue for transplantation is imperative if the procedure is to be widely adopted in the clinical domain. A number of possibilities are currently being explored experimentally (see Table 1), although all of them present difficulties that must be overcome before they can be adopted clinically (reviewed in ref. 6). Table 1 Alternatives to Primary Human Neuronal Cells for Transplantation in PD Dopamine-containing polymers that release dopamine slowly over months/years. Catecholamine-producing cells found naturally within the adult, which may thus be suitable for autotransplantation, e.g., adrenal medulla, carotid body, superior cervical ganglion. Catecholamine-producing cell lines that may be encapsulated to prevent rejection and spread of the tumour cells out into the host brain, e.g., PC12 cells. Cells transfected with tyrosine hydroxylase, which potentially allows for the possibility of autotransplantation, e.g., skin fibroblasts. Xenografts of dopamine-rich tissue, e.g., embryonic porcine ventral mesencephalic tissue. Neural stem cells. Embryonic stem (ES) cells. |
