Journal Article

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

Ivar Mendez, Rosario Sanchez-Pernaute, Oliver Cooper, Angel Viñuela, Daniela Ferrari, Lars Björklund, Alain Dagher and Ole Isacson

in Brain

Published on behalf of The Guarantors of Brain

Volume 128, issue 7, pages 1498-1510
Published in print July 2005 | ISSN: 0006-8950
Published online May 2005 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/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

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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.

Keywords: transplantation; dopamine neuron; Parkinson's disease; 18F-DOPA = 18F-fluorodopa; GDNF = glial-derived neurotrophic factor; GFAP = glial fibrillary acidic protein; Girk2 = G-protein-coupled inward rectifying current potassium channel type 2; PBS = phosphate buffered saline; SN = substantia nigra; SNc = substantia nigra pars compacta; TH = tyrosine hydroxylase; UPDRS = Unified Parkinson's Disease Rating Scale

Journal Article.  9536 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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