Efficient early and sustained transduction of human fetal mesencephalon using adeno-associated virus type 2 vectors.

Détails

ID Serval
serval:BIB_1C95D8A6EC31
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Efficient early and sustained transduction of human fetal mesencephalon using adeno-associated virus type 2 vectors.
Périodique
Cell Transplantation
Auteur⸱e⸱s
Tenenbaum L., Peschanski M., Melas C., Rodesh F., Lehtonen E., Stathopoulos A., Velu T., Brotchi J., Levivier M.
ISSN
0963-6897 (Print)
ISSN-L
0963-6897
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
13
Numéro
5
Pages
565-571
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The success of transplantation of human fetal mesencephalic tissue into the putamen of patients with Parkinson's disease (PD) is still limited by the poor survival of the graft. In animal models of fetal transplantation for PD, antiapoptotic agents, such as growth factors or caspase inhibitors, or agents counteracting oxidative stress enhance the survival and reinnervation potential of the graft. Genetic modification of the transplant could allow a local and continuous delivery of these factors at physiologically relevant doses. The major challenge remains the development of strategies to achieve both early and sustained gene delivery in the absence of vector-mediated toxicity. We recently reported that E14 rat fetal mesencephalon could be efficiently tranduced by adeno-associated virus type 2 (AAV2) vectors and that gene expression was maintained until at least 3 months after transplantation in the adult rat striatum. Here we report that an AAV2 vector can mediate the expression of the EGFP reporter gene under the control of a CMV promoter in organotypic cultures of freshly explanted solid fragments of human fetal mesencephalic tissue as early as 3 days to at least 6 weeks postinfection. These results suggest that AAV2 vectors could be used to genetically modify the human fetal tissue prior to transplantation to Parkinson's patients to promote graft survival and integration.
Mots-clé
Animals, Brain Tissue Transplantation/methods, Cell Transplantation/methods, Culture Media, Cytomegalovirus/genetics, Dependovirus/genetics, Fetal Tissue Transplantation/methods, Gene Expression Regulation, Gene Transfer Techniques, Genetic Therapy/methods, Genetic Vectors, Green Fluorescent Proteins/genetics, Humans, Mesencephalon/cytology, Parkinson Disease/therapy, Promoter Regions, Genetic, Rats, Recombinant Proteins/metabolism, Time Factors, Transduction, Genetic
Pubmed
Web of science
Création de la notice
20/01/2008 18:35
Dernière modification de la notice
20/08/2019 13:53
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