Viral gene transfer for bone healing

Objectives

Local gene transfer to bone and adjacent tissues offers promise in cases of bone healing disorders such as segmental bone defects, non-unions, and aseptic loosening of endoprotheses.

Method and results

Studies in which osteoinductive genes have been administered therapeutically are predominantly segmental defect models in rabbits and rats. One additional study has been performed to prevent bone loss in mice.

The administration of different marker genes to segmental defects induced transient gene expression locally for up to 6 weeks. β-galactosidase expression was seen after injection of adenoviral vectors encoding the LacZ gene within the callus tissue, the bony ends adjacent to the cuts, and the surrounding muscle. After injection of Ad-luciferase gene expression was also found predominantly locally, and besides that very low expression in the liver for up to 5 days, whereas local expression within bone lasted up to 6, within the surrounding soft tissues up to 3 weeks. No transgene expression was seen in the contralateral limb, lung, or spleen.

Injection of adenoviral vectors carrying BMP-2 cDNA led to healing of the segmental defects after 8–12 weeks, the untreated control defects did not heal. Vectors encoding the transforming growth factor-β1 gene increased matrix formation within the defects, but resulted not in complete mineralization of the newly formed callus as seen after transduction with the BMP-2 cDNA. The results were judged by radiographic, histologic, histomorphologic, and biomechanical criteria.

Conclusion

The data encourage the further development of genetic approaches to enhancing bone formation in cases of bone disorders.