Survival of genetically engineered, adult-derived rat astrocytes grafted into the 6-hydroxydopamine lesioned adult rat striatum.
Astrocytes are potentially useful as vehicles for gene transfer into the CNS. As endogenous CNS cells, they possess secretory mechanisms and can be grown in vitro. We have developed an animal model of this system using autologous astrocyte grafts in Fischer 344 rats. Cultured cells were infected with an adenoviral vector containing the reporter gene lacZ in vitro and then grafted into the striatum of adult Fischer 344 rats previously lesioned with 6-OHDA. Survival of the cells and activity of the beta-galactosidase protein were followed for up to 21 days after injection. The grafted cells were shown to survive throughout the experimental period although the expression of transgene was reduced with time. If long-term expression of therapeutically active substances can be achieved, grafts of adult-derived astrocytes genetically engineered using recombinant adenoviral vectors could be employed in the treatment of Parkinson's disease and other neurological disorders.
Ljungberg
M C
MC
Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AZ, UK.
Stern
G
G
Wilkin
G P
GP
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000637:transplantation*; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000601:surgery*; D003913:Dextroamphetamine / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins; D064231:Nestin; D016627:Oxidopamine; D051381:Rats; D011916:Rats, Inbred F344; D014746:Vimentin / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D014746:Vimentin; D016627:Oxidopamine; D001616:beta-Galactosidase; D003913:Dextroamphetamine