Stem cells for cell therapy in Parkinson's disease

Clinical studies with intrastriatal transplants of human embryonic mesencephalic tissue have provided proof-of-principle for the cell replacement strategy in Parkinson's disease (PD) patients. The grafted dopaminergic neurons can reinnervate the denervated striatum. restore regulated dopamine (DA) release and movement-related frontal cortical activation. and give rise to significant symptomatic relief. However, there are several problems linked to the use of primary, embryonic tissue: (i) lack of sufficient amounts of tissue for transplantation in a large number of patients: (ii) variability of functional outcome, with some patients showing major improvement and others modest if any clinical benefit: (iii) occurrence of troublesome dyskinesias in a significant proportion of patients after transplantation. Stem cells could be useful to generate large numbers of DA neurons in standardized and quality-controlled preparations. So far, neurons with at least some dopaminergic characteristics have been generated from stein cells. However. in most cases their survival after grafting in animal PD models has been poor and it is also unclear if they, function as normal mesencephalic DA neurons. For the development of a clinically useful cell therapy in PD. it is also necessary to define better criteria for patient selection and how graft placement should be optimized in each patient. Several scientific issues need to be addressed before stem cell-based therapies can be tested in PD patients. (C) 2003 Elsevier Science Ltd. All rights reserved.