Effect of cell-based VEGF gene therapy on healing of a segmental bone defect.
Fracture healing requires coordinated coupling between osteogenesis and angiogenesis in which vascular endothelial growth factor (VEGF) plays a key role. We hypothesized that targeted over-expression of angiogenic and osteogenic factors within the fracture would promote bone healing by inducing development of new blood vessels and stimulating/affecting proliferation, survival, and activity of skeletal cells. Using a cell-based method of gene transfer, without viral vector, 5.0 x 10(6) fibroblasts transfected with VEGF were delivered to a 10-mm bone defect in rabbit tibiae (Group 1) (n = 9); control groups were treated with fibroblasts (Group 2) (n = 7), or saline (Group 3) (n = 7) only. After 12 weeks, eight tibial fractures healed in Group 1, compared to four each in Groups 2 and 3. In Group 1, ossification was seen across the entire defect; in Groups 2 and 3, the defects were fibrous and sparsely ossified. Group 1 had more positively stained (CD31) vessels than Groups 2 and 3. MicroCT 3-D showed complete bridging of the new bone for Group 1, but incomplete healing for Groups 2 and 3. MicroCT bone structural parameters showed significant differences between VEGF treatment and control groups (p < 0.05). These results indicate that the cell-based VEGF gene therapy has significant angiogenic and osteogenic effects to enhance healing of a segmental defect in the long bone of rabbits.
Li
Ru
R
St. Michael's Hospital, University of Toronto, Ontario, Canada.
Stewart
Duncan J
DJ
von Schroeder
Herbert P
HP
Mackinnon
Erin S
ES
Schemitsch
Emil H
EH
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D020405:Dermis / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D017102:Fracture Healing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D009389:Neovascularization, Pathologic; D010012:Osteogenesis; D011817:Rabbits; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A