Abstract
This study aimed to investigate whether adenovirus-mediated VEGF gene therapy could improve bone healing, and it compared the effects of an in vivo versus ex vivo approach using rats. A replication-deficient adenovirus containing human VEGF165 and green fluorescence protein (GFP) genes AdGFP/hVEGF165 was used in this study. The rats were divided into 5 groups, and a bone fracture model was used in all of the rats. In the in vivo group, the adenovirus particles were directly injected infraperiosteally. In the ex vivo group, the rat bone marrow stromal cells (BMSC) that had been infected by AdGFP/hVEGF165 in vitro were seeded onto a resorbable matrix and used to treat the bone fracture by injection infraperiosteally at specific anatomic sites. Three groups served as control subjects. Two groups were treated either with adenovirus containing green fluorescence protein gene (AdGFP) or with BMSCs that had been transfected by AdGFP. Another group was left untreated. Fracture healing was evaluated radiographically and histologically. The results showed that VEGF gene treated rats had more ossification at the fracture site than did the control groups 2 weeks after surgery. Both ex vivo and in vivo group showed extensively ossification, and the newly formed bone exhibited normal bone histology at 28 days after surgery. There was no difference in the union of the bone between the in vivo and the ex vivo group. In summary, we have demonstrated that VEGF gene therapy can enhance bone fracture healing, and both the in vivo and ex vivo approaches may be effective and suitable for introducing this transgene to the fracture site.
