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. © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved

Mendez, I., Sanchez-Pernaute, R., Cooper, O., Viñuela, A., Ferrari, D., Björklund, L., et al. (2005). Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. BRAIN, 128(7), 1498-1510 [10.1093/brain/awh510].

Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease

Ferrari, D;
2005

Abstract

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. © The Author (2005). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved
Articolo in rivista - Articolo scientifico
Dopamine neuron; Parkinson's disease; Transplantation; Aged; Autopsy; Biomarkers; Brain Chemistry; Calbindins; Cell Survival; Corpus Striatum; Dopamine; Female; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Graft Survival; Humans; Immunohistochemistry; Male; Mesencephalon; Middle Aged; Neurons; Parkinson Disease; Positron-Emission Tomography; Potassium Channels, Inwardly Rectifying; S100 Calcium Binding Protein G; Substantia Nigra; Tyrosine 3-Monooxygenase; Brain Tissue Transplantation; Fetal Tissue Transplantation; Neuroscience (all)
English
1498
1510
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Mendez, I., Sanchez-Pernaute, R., Cooper, O., Viñuela, A., Ferrari, D., Björklund, L., et al. (2005). Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. BRAIN, 128(7), 1498-1510 [10.1093/brain/awh510].
Mendez, I; Sanchez-Pernaute, R; Cooper, O; Viñuela, A; Ferrari, D; Björklund, L; Dagher, A; Isacson, O
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/107200
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