Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease.
We report the first post-mortem analysis of two patients with Parkinson's disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive 18F-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (n = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3-4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation.
Mendez
Ivar
I
Dalhousie University and Queen Elizabeth II Health Science Center, Division of Neurosurgery and Neuroscience, Halifax, Canada.
Sanchez-Pernaute
Rosario
R
Cooper
Oliver
O
Viñuela
Angel
A
Ferrari
Daniela
D
Björklund
Lars
L
Dagher
Alain
A
Isacson
Ole
O
D000368:Aged; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D001923:Brain Chemistry; D016380:Brain Tissue Transplantation; D064026:Calbindins; D002470:Cell Survival; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000473:pathology; D004298:Dopamine / Q000032:analysis / Q000502:physiology*; D005260:Female; D016332:Fetal Tissue Transplantation; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000473:pathology / Q000637:transplantation*; D008875:Middle Aged; D009474:Neurons / Q000502:physiology / Q000637:transplantation; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery*; D049268:Positron-Emission Tomography; D024661:Potassium Channels, Inwardly Rectifying / Q000032:analysis; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D015415:Biomarkers; D064026:Calbindins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497069:Kcnj6 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying; D064030:S100 Calcium Binding Protein G; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine