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Cell Rep. 2014 Jun 26;7(6):1755-61. doi: 10.1016/j.celrep.2014.05.027. Epub 2014 Jun 6.

Long-term health of dopaminergic neuron transplants in Parkinson's disease patients.

Author information

  • 1Neuroregeneration Research Institute, Harvard University and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA.
  • 2Division of Neurosurgery, Department of Anatomy and Neurobiology, and Department of Pharmacology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS B3H 3A7, Canada.
  • 3Neuroregeneration Research Institute, Harvard University and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. Electronic address: isacson@hms.harvard.edu.

Abstract

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.

PMID:
24910427
PMCID:
PMC4105701
DOI:
10.1016/j.celrep.2014.05.027
[PubMed - indexed for MEDLINE]
Free PMC Article
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