Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation

✍ Scribed by Henning Madry; Greg Emkey; David Zurakowski; Stephen B Trippel

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 230 KB
• Volume: 6
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.488

✦ Synopsis

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.