Nature Medicine
11, 291 - 297 (2005)
Published online: 13 February 2005; | doi:10.1038/nm1190
Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapyHiromu Ito1, 2, Mette Koefoed1, 3, Prarop Tiyapatanaputi1, Kirill Gromov1, 3, J Jeffrey Goater1, Jonathan Carmouche1, Xinping Zhang1, Paul T Rubery1, Joseph Rabinowitz4, R Jude Samulski4, 5, Takashi Nakamura2, Kjeld Soballe3, Regis J O'Keefe1, Brendan F Boyce1
& Edward M Schwarz11
The Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA. 2
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo, Kyoto 606-8507, Japan. 3
The Department of Orthopedics, University Hospital of Aarhus, Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark. 4
Gene Therapy Center, University of North Carolina, 7119 Thurston Building, CB# 7352 Chapel Hill, North Carolina 27599, USA. 5
Department of Pharmacology, University of North Carolina, 7119 Thurston Building, CB# 7352 Chapel Hill, North Carolina 27599, USA.
Correspondence should be addressed to Edward M Schwarz edward_schwarz@urmc.rochester.eduStructural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze-dried onto the cortical surface without losing infectivity. We show that combination rAAV-RANKL- and rAAV-VEGF-coated allografts show marked remodeling and vascularization, which leads to a new bone collar around the graft. In conclusion, we find that RANKL and VEGF are necessary and sufficient for efficient autograft remodeling and can be transferred using rAAV to revitalize structural allografts.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
