C. Shults et al., Fibroblast growth factor-2-producing fibroblasts protect the nigrostriataldopaminergic system from 6-hydroxydopamine, BRAIN RES, 883(2), 2000, pp. 192-204
We tested the hypothesis that fibroblasts. which had been genetically engin
eered to produce fibroblast growth factor-2 (FGF-2), can protect nigrostria
tal dopaminergic neurons. Three groups of rats received either a burr hole
only (n=5) or implantation of fibroblasts, which had been genetically engin
eered to produce beta -galactosidase (beta -gal) (n=8) or FGF-2 (n=8), at t
wo sites in the right striatum. Two weeks Inter, the animals received an in
jection of 25 mug of 6-hydroxydopamine hydrobromide (6-OHDA) midway between
the two implant sites. The group that received FGF-2-fibroblasts had signi
ficantly fewer apomorphine-induced rotations than the groups that received
a burr hole only or beta -gal-fibroblasts at weeks 2 and 3 following lesion
ing with 6-OHDA. Testing for amphetamine-induced rotation revealed a mild r
eduction in rotation in the beta -gal-fibroblast group compared to the burr
hole only group, but a striking attenuation of amphetamine-induced rotatio
n in the FGF-2-fibroblast group. There was also preservation of TH-IR neuro
ns on the lesioned side relative to both control groups, The size of the gr
afts and the gliosis surrounding the injection sites did not differ between
the FGF-2-fibroblast and beta -gal-fibroblast groups. To further character
ize the production of FGF-2 by the FGF-2-fibroblasts, we implanted FGF-2-fi
broblasts and beta -gal-fibroblast into the striatum of rats but did not le
sion the animals with 6-OHDA. The animals were then sacrificed at 1, 2 and
5 weeks following implantation. Prior to implantation the FGF-2 fibroblasts
contained 148 ng/mg of FGF-2-immunoreactive (FGF-2-IR) material per mg of
protein of cell lysate. After implantation FGF-2-IR material was noted in t
he grafts of FGF-2-fibroblasts, most conspicuously at 1 and 2 weeks followi
ng implantation. We also noted FGF-2-IR material in the nuclei of reactive
astrocytes adjacent to the implants, and OX-42-immunoreactive (OX-42-IR) ce
lls adjacent and occasionally within the implants. Our work indicates that
fibroblasts genetically engineered to produce FGF-2 and implanted in the st
riatum can protect the nigrostriatal dopaminergic system and may be useful
in the treatment of Parkinson's disease. (C) 2000 Elsevier Science B.V. All
rights reserved.