RRC ID |
33955
|
著者 |
Yamada H, Dezawa M, Shimazu S, Baba M, Sawada H, Kuroiwa Y, Yamamoto I, Kanno H.
|
タイトル |
Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease.
|
ジャーナル |
Ann Neurol
|
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.
|
巻・号 |
54(3)
|
ページ |
352-9
|
公開日 |
2003-9-1
|
DOI |
10.1002/ana.10672
|
PMID |
12953267
|
MeSH |
Animals
Brain Tissue Transplantation
Cell Differentiation / physiology
Cells, Cultured
Corpus Striatum / cytology
Corpus Striatum / physiology
Corpus Striatum / transplantation*
Dopamine / metabolism
Embryo, Mammalian
Fetal Tissue Transplantation
Graft Survival
Humans
Immunohistochemistry
Ligases / genetics*
Male
Models, Animal
Motor Activity / physiology
Neurons / cytology
Neurons / physiology
Neurons / transplantation*
Oxidopamine
Parkinsonian Disorders / chemically induced
Parkinsonian Disorders / therapy*
Rats
Rats, Sprague-Dawley
Stem Cell Transplantation*
Stem Cells / cytology
Stem Cells / metabolism
Transduction, Genetic
Tumor Suppressor Proteins*
Ubiquitin-Protein Ligases*
Von Hippel-Lindau Tumor Suppressor Protein
|
IF |
9.037
|
引用数 |
24
|
WOS 分野
|
CLINICAL NEUROLOGY
NEUROSCIENCES
|
リソース情報 |
遺伝子材料 |
Ax1 CA gfp (RDB01727) |