Long-Term Health of Dopaminergic Neuron Transplants in Parkinson's Disease Patients

To determine the long-term health and function of transplanted dopamine neurons in Parkinson’s disease (PD) patients, the expression of dopamine transporters (DATs) and mitochondrial morphology were examined in human fetal midbrain cellular transplants. DAT was robustly expressed in transplanted dopamine neuron terminals in the reinnervated host putamen and caudate for at least 14 years after transplantation. The transplanted dopamine neurons showed a healthy and nonatrophied morphology at all time points. Labeling of the mitochondrial outer membrane protein Tom20 and α-synuclein showed a typical cellular pathology in the patients’ own substantia nigra, which was not observed in transplanted dopamine neurons. These results show that the vast majority of transplanted neurons remain healthy for the long term in PD patients, consistent with clinical findings that fetal dopamine neuron transplants maintain function for up to 15–18 years in patients. These findings are critically important for the rational development of stem-cell-based dopamine neuronal replacement therapies for PD. [Display omitted] •DAT expression is maintained for 4–14 years after transplantation in the PD brain•No abnormal mitochondrial localization is observed in transplanted dopamine neurons•Grafted human fetal dopamine neurons remain healthy and functional for the long term A postmortem evaluation of fetal midbrain neurons transplanted 4–14 years earlier in patients with Parkinson’s disease revealed that the dopamine neurons were free of obvious mitochondrial pathology or α-synuclein-like aggregates. Moreover, the important dopamine transporter that is responsible for synaptic reuptake of dopamine at the synapse responsible for movement initiation was robustly expressed for at least 14 years after transplantation on axons reinnervating the host brain putamen region. These data provide a foundation for developing cell therapies for patients with Parkinson’s disease and suggest that equivalent stem-cell-derived midbrain dopamine neurons can provide a long-term benefit.