Gene transfer to the central nervous system by transplantation of cerebral endothelial cells.
A cerebral endothelial immortalized cell line was used in transplantation experiments to deliver gene products to the adult rat brain. Survival of grafted cells was observed for at least 1 year, without any sign of tumor formation. When genetically modified to express bacterial beta-galactosidase and transplanted into the striatum, these cells were shown, by light and electron microscope analysis, to integrate into the host brain parenchyma and microvasculature. Following implantation into the striatum and nucleus basalis of adult rats, endothelial cells engineered to secrete mouse beta-nerve growth factor (NGF) induced the formation of a dense network of low-affinity NGF receptor-expressing fibers near the implantation sites. This biological response was observed from 3 to 8 weeks after engraftment. The present study establishes the cerebral endothelial cell as an efficient vector for gene transfer to the central nervous system.
Quinonéro
J
J
U-134 INSERM, Paris, France.
Tchélingérian
J L
JL
Vignais
L
L
Foignant-Chaverot
N
N
Colin
C
C
Horellou
P
P
Liblau
R
R
Barbin
G
G
Strosberg
A D
AD
Jacque
C
C
Couraud
P O
PO
D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D016380:Brain Tissue Transplantation; D018929:Cell Culture Techniques; D002460:Cell Line; D003342:Corpus Striatum / Q000648:ultrastructure; D004727:Endothelium / Q000637:transplantation; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D006085:Graft Survival; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D009414:Nerve Growth Factors; D001616:beta-Galactosidase