ParkinsonCanadaV1, Main, Exploration, bibRecord, 002F44

Complications of a trophic xenotransplant approach in parkinsonian monkeys

Identifieur interne : 002F44 ( Main/Exploration ); précédent : 002F43; suivant : 002F45

Complications of a trophic xenotransplant approach in parkinsonian monkeys

Auteurs : Pierre J. Blanchet [États-Unis, Canada] ; Spiros Konitsiotis [États-Unis, Grèce] ; Hideki Mochizuki [États-Unis, Japon] ; Ryszard Pluta [États-Unis] ; Dwaine F. Emerich [États-Unis] ; Thomas N. Chase [États-Unis] ; M. Maral Mouradian [États-Unis]

Source :

Progress in neuro-psychopharmacology & biological psychiatry [ 0278-5846 ] ; 2003.

RBID : Pascal:03-0390767

Descripteurs français

Pascal (Inist)
- Parkinson maladie, Facteur GDNF, Transplantation, Cellule, Encapsulation, Thérapie génique, Chimiothérapie, Traitement, Implant, Efficacité traitement, Complication, Toxicité, Animal, Singe, Corps strié, Activité biologique, Encéphale, Système nerveux central, Long terme, Lignée BHK.
Wicri :
- topic : Singe.

English descriptors

KwdEn :
- Animal, Biological activity, Brain (vertebrata), Cell, Central nervous system, Chemotherapy, Complication, Corpus striatum, Encapsulation, Gene therapy, Glial cell line derived neurotrophic factor, Implant, Long term, Monkey, Parkinson disease, Toxicity, Transplantation, Treatment, Treatment efficiency.

Abstract

Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.

Affiliations:

Canada, Grèce, Japon, États-Unis
Tokyo

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Le document en format XML

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<front><div type="abstract" xml:lang="en">Various restorative cell transplantation strategies have been investigated to substitute for lost dopamine (DA) neurons or to enhance DA synthesis in Parkinson's disease. Intracerebral implantation of engineered cells encapsulated in a semipermeable polymer membrane constitutes one way to deliver bioactive substances unable to cross the blood-brain barrier while avoiding the need for long-term immunosuppression. Glial cell line-derived neurotrophic factor (GDNF) has shown trophic effects on DA neurons but effective and sustained delivery within the brain parenchyma remains problematic. The long-term efficacy and late complications of a xenotransplant approach utilizing GDNF-expressing encapsulated baby hamster kidney (BHK) cells were examined. Each of five MPTP-lesioned parkinsonian cynomolgus monkeys received five devices containing active or inert cells grafted bilaterally in the striatum in a two-stage procedure 9 months apart and animals were sacrificed 4 months later for analyses. No definite motor benefit was observed, DA levels were comparable between GDNF- and control cell-implanted striata, and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra showed no consistent recovery. Cell viability and GDNF synthesis in the explanted devices were negligible. The brain tissue surrounding all implants showed an intense immune reaction with prominent "foreign body" inflammatory infiltrates. Membrane biophysics, the cell type used, and the extended period of time the devices remained in situ may have contributed to the negative outcome and should be addressed in future investigations using this approach.</div>
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	La maladie de Parkinson au Canada (serveur d'exploration)
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La maladie de Parkinson au Canada (serveur d'exploration)

Complications of a trophic xenotransplant approach in parkinsonian monkeys

Complications of a trophic xenotransplant approach in parkinsonian monkeys

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Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

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