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Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease
- Source :
- Annals of Neurology. 54:352-359
- Publication Year :
- 2003
- Publisher :
- Wiley, 2003.
-
Abstract
- Neuronal progenitor cells (NPCs) may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is low. We transduced the von Hippel-Lindau (VHL) gene into NPCs isolated from embryonic rat brain. The NPCs with the transduced VHL gene efficiently differentiated into tyrosine hydroxylase-positive neurons in vitro. NPCs with the transduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine-tyrosine hydroxylase double-labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within the host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine-induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that a sufficient number of dopaminergic neurons can develop from them to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD.
- Subjects :
- Male
Parkinson's disease
Dopamine
Ubiquitin-Protein Ligases
Striatum
Motor Activity
urologic and male genital diseases
Ligases
Rats, Sprague-Dawley
chemistry.chemical_compound
Parkinsonian Disorders
Fetal Tissue Transplantation
Transduction, Genetic
otorhinolaryngologic diseases
medicine
Animals
Humans
Brain Tissue Transplantation
Progenitor cell
Oxidopamine
Cells, Cultured
Neurons
business.industry
Stem Cells
Tumor Suppressor Proteins
Graft Survival
Genetic transfer
Dopaminergic
Cell Differentiation
Embryo, Mammalian
medicine.disease
Immunohistochemistry
Embryonic stem cell
Corpus Striatum
Rats
Cell biology
Transplantation
stomatognathic diseases
nervous system
Neurology
chemistry
Von Hippel-Lindau Tumor Suppressor Protein
Models, Animal
Neurology (clinical)
business
Neuroscience
Stem Cell Transplantation
Subjects
Details
- ISSN :
- 15318249 and 03645134
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Annals of Neurology
- Accession number :
- edsair.doi.dedup.....67f8d045ef8eefda6a07be9d42958972