Clinical translation of stem cell transplantation in Parkinson's disease

Journal of Internal Medicine
O Lindvall

Abstract

In Parkinson's disease (PD), the main pathology underlying the motor symptoms is a loss of nigrostriatal dopaminergic neurons. Clinical trials of intrastriatal transplantation of human foetal mesencephalic tissue have shown that the grafted dopaminergic neurons re-innervate the striatum, restore striatal dopamine release and, in some cases, induce major, long-lasting improvement of motor function. However, nonmotor symptoms originating from degeneration outside the striatum or in nondopaminergic systems are not alleviated by intrastriatal implantation of dopaminergic neurons. Stem cells and reprogrammed cells could potentially be used to produce dopaminergic neurons for transplantation in patients with PD. Recent studies demonstrate that standardized preparations of dopaminergic neurons of the correct substantia nigra phenotype can be generated from human embryonic stem cells in large numbers, and they will soon be available for patient application. In addition, dopaminergic neurons derived from human induced pluripotent stem cells are being considered for clinical translation. Important challenges include the demonstration of potency (growth capacity and functional efficacy) and safety of the generated dopaminergic neurons in ...Continue Reading

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