Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation.
BACKGROUND
Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation.


METHODS
Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli beta-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants.


RESULTS
The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [(3)H]thymidine and [(35)S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis.


CONCLUSIONS
These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal.
Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg, Germany. hmad@hotmail.com
Henning
H
Madry
Greg
G
Emkey
David
D
Zurakowski
Stephen B
SB
Trippel
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism / Q000637:transplantation*; D002417:Cattle; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D019902:Chondrocytes / Q000378:metabolism / Q000637:transplantation*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D008954:Models, Biological; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D013936:Thymidine