Intracerebral transplantation and successful integration of astrocytes following genetic modification with a high-capacity adenoviral vector.
To investigate the ability of genetically modified astrocytes to integrate into adult rat brain, two spontaneously immortalized cell lines and the allogenic nontumorigenic glioma cell line F98 were transduced with a high-capacity adenoviral vector (HC-Adv) expressing the EGFP gene from the hCMV promoter. In organotypic slice cultures the transduced astrocytes were shown to integrate into the brain tissue. Following transplantation of the transduced astrocytes into the striatum of adult rats, the transplanted cells survived at least for 6 weeks, continuously expressed the EGFP transgene, in close neighborhood with cells of the recipient tissue executing their differentiation capacity along the glial lineage. Thus, HC-Adv transduced astrocytes are promising vehicles to locally deliver therapeutic proteins for the treatment of neurodegenerative diseases.
Arnhold
S
S
Department of Anatomy I, University of Cologne, Joseph-Stelzmann Str. 9, 50931 Köln, Germany. stefan.arnhold@uni-koeln.de
Kreppel
F
F
Kandirali
S
S
Lenartz
D
D
Klinz
F J
FJ
Sturm
V
V
Kochanek
S
S
Andressen
C
C
Addicks
K
K
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D019070:Cell Lineage / Q000235:genetics; D048429:Cell Size / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D017690:Cell Transplantation / Q000379:methods* / Q000639:trends; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000254:growth & development / Q000637:transplantation; D005333:Fetus; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000235:genetics*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*
D005904:Glial Fibrillary Acidic Protein; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins