Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease
Identifieur interne : 002A71 ( Main/Exploration ); précédent : 002A70; suivant : 002A72Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease
Auteurs : Ivar Mendez ; Rosario Sanchez-Pernaute [États-Unis] ; Oliver Cooper [États-Unis] ; Angel Vin Uela [États-Unis] ; Daniela Ferrari [États-Unis] ; Lars Bjo Rklund [États-Unis] ; Alain Dagher [Canada] ; Ole Isacson [États-Unis]Source :
- Brain [ 0006-8950 ] ; 2005-07.
English descriptors
- KwdEn :
- 18F-DOPA = 18F-fluorodopa, Aged, Autopsy, Biomarkers (analysis), Brain Chemistry, Brain Tissue Transplantation, Calbindins, Cell Survival, Corpus Striatum (diagnostic imaging), Corpus Striatum (pathology), Dopamine (analysis), Dopamine (physiology), Female, Fetal Tissue Transplantation, G Protein-Coupled Inwardly-Rectifying Potassium Channels, GDNF = glial-derived neurotrophic factor, GFAP = glial fibrillary acidic protein, Girk2 = G-protein-coupled inward rectifying current potassium channel type 2, Graft Survival, Humans, Immunohistochemistry (methods), Male, Mesencephalon (diagnostic imaging), Mesencephalon (pathology), Mesencephalon (transplantation), Middle Aged, Neurons (physiology), Neurons (transplantation), PBS = phosphate buffered saline, Parkinson Disease (diagnostic imaging), Parkinson Disease (pathology), Parkinson Disease (surgery), Parkinson's disease, Positron-Emission Tomography, Potassium Channels, Inwardly Rectifying (analysis), S100 Calcium Binding Protein G (analysis), SN = substantia nigra, SNc = substantia nigra pars compacta, Substantia Nigra (diagnostic imaging), Substantia Nigra (pathology), TH = tyrosine hydroxylase, Tyrosine 3-Monooxygenase (analysis), UPDRS = Unified Parkinson's Disease Rating Scale, dopamine neuron, transplantation.
- MESH :
- chemical , analysis : Biomarkers, Dopamine, Potassium Channels, Inwardly Rectifying, S100 Calcium Binding Protein G, Tyrosine 3-Monooxygenase.
- diagnostic imaging : Corpus Striatum, Mesencephalon, Parkinson Disease, Substantia Nigra.
- methods : Immunohistochemistry.
- pathology : Corpus Striatum, Mesencephalon, Parkinson Disease, Substantia Nigra.
- chemical , physiology : Dopamine, Neurons.
- surgery : Parkinson Disease.
- transplantation : Mesencephalon, Neurons.
- Aged, Autopsy, Brain Chemistry, Brain Tissue Transplantation, Calbindins, Cell Survival, Female, Fetal Tissue Transplantation, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Graft Survival, Humans, Male, Middle Aged, Positron-Emission Tomography.
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.
Url:
- https://api-v5.istex.fr/document/FB9B1A34E60F8510289D1B31E92CD657F198C2C7/fulltext/pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610438
DOI: 10.1093/brain/awh510
Affiliations:
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type="state">Québec</region></placeName></affiliation><affiliation></affiliation></author><author><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard University and McLean Hospital, NINDS Udall Parkinson's Disease Research Center of Excellence, Belmont, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><title level="j" type="abbrev">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2005-07">2005-07</date><biblScope unit="volume">128</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="1498">1498</biblScope><biblScope unit="page" to="1510">1510</biblScope></imprint><idno type="ISSN">0006-8950</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>18F-DOPA = 18F-fluorodopa</term><term>Aged</term><term>Autopsy</term><term>Biomarkers (analysis)</term><term>Brain Chemistry</term><term>Brain Tissue Transplantation</term><term>Calbindins</term><term>Cell Survival</term><term>Corpus Striatum (diagnostic imaging)</term><term>Corpus Striatum (pathology)</term><term>Dopamine (analysis)</term><term>Dopamine (physiology)</term><term>Female</term><term>Fetal Tissue Transplantation</term><term>G Protein-Coupled Inwardly-Rectifying Potassium Channels</term><term>GDNF = glial-derived neurotrophic factor</term><term>GFAP = glial fibrillary acidic protein</term><term>Girk2 = G-protein-coupled inward rectifying current potassium channel type 2</term><term>Graft Survival</term><term>Humans</term><term>Immunohistochemistry (methods)</term><term>Male</term><term>Mesencephalon (diagnostic imaging)</term><term>Mesencephalon (pathology)</term><term>Mesencephalon (transplantation)</term><term>Middle Aged</term><term>Neurons (physiology)</term><term>Neurons (transplantation)</term><term>PBS = phosphate buffered saline</term><term>Parkinson Disease (diagnostic imaging)</term><term>Parkinson Disease (pathology)</term><term>Parkinson Disease (surgery)</term><term>Parkinson's disease</term><term>Positron-Emission Tomography</term><term>Potassium Channels, Inwardly Rectifying (analysis)</term><term>S100 Calcium Binding Protein G (analysis)</term><term>SN = substantia nigra</term><term>SNc = substantia nigra pars compacta</term><term>Substantia Nigra (diagnostic imaging)</term><term>Substantia Nigra (pathology)</term><term>TH = tyrosine hydroxylase</term><term>Tyrosine 3-Monooxygenase (analysis)</term><term>UPDRS = Unified Parkinson's Disease Rating Scale</term><term>dopamine neuron</term><term>transplantation</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Biomarkers</term><term>Dopamine</term><term>Potassium Channels, Inwardly Rectifying</term><term>S100 Calcium Binding Protein G</term><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Corpus Striatum</term><term>Mesencephalon</term><term>Parkinson Disease</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Immunohistochemistry</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term><term>Mesencephalon</term><term>Parkinson Disease</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Dopamine</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Mesencephalon</term><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Autopsy</term><term>Brain Chemistry</term><term>Brain Tissue Transplantation</term><term>Calbindins</term><term>Cell Survival</term><term>Female</term><term>Fetal Tissue Transplantation</term><term>G Protein-Coupled Inwardly-Rectifying Potassium Channels</term><term>Graft Survival</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Positron-Emission Tomography</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Massachusetts</li><li>Québec</li></region><settlement><li>Montréal</li></settlement></list><tree><noCountry><name sortKey="Mendez, Ivar" sort="Mendez, Ivar" uniqKey="Mendez I" first="Ivar" last="Mendez">Ivar Mendez</name></noCountry><country name="États-Unis"><region name="Massachusetts"><name sortKey="Sanchez Pernaute, Rosario" sort="Sanchez Pernaute, Rosario" uniqKey="Sanchez Pernaute R" first="Rosario" last="Sanchez-Pernaute">Rosario Sanchez-Pernaute</name></region><name sortKey="Bjo Rklund, Lars" sort="Bjo Rklund, Lars" uniqKey="Bjo Rklund L" first="Lars" last="Bjo Rklund">Lars Bjo Rklund</name><name sortKey="Cooper, Oliver" sort="Cooper, Oliver" uniqKey="Cooper O" first="Oliver" last="Cooper">Oliver Cooper</name><name sortKey="Ferrari, Daniela" sort="Ferrari, Daniela" uniqKey="Ferrari D" first="Daniela" last="Ferrari">Daniela Ferrari</name><name sortKey="Isacson, Ole" sort="Isacson, Ole" uniqKey="Isacson O" first="Ole" last="Isacson">Ole Isacson</name><name sortKey="Vin Uela, Angel" sort="Vin Uela, Angel" uniqKey="Vin Uela A" first="Angel" last="Vin Uela">Angel Vin Uela</name></country><country name="Canada"><region name="Québec"><name sortKey="Dagher, Alain" sort="Dagher, Alain" uniqKey="Dagher A" first="Alain" last="Dagher">Alain Dagher</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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