Abstract
A segmental bone fracture generally necessitates extended and complicated surgical methods related to bone and vessel reconstruction, thus autologous or allogenic bone grafting is usually required.Recently, mesenchymal stem cells (MSCs)-based cell therapy and virus-based gene therapy have converged and have shown great potential in assisting and accelerating bone healing. Baculovirus is a novel vector for gene delivery into stem cells, but it only mediates transient expression. Therefore we developed a long-term system whereby one baculovirus expressed FLP recombinase (Bac-FLP) while the other hybrid baculovirus harbored an Frt flanking transgene cassette to assist and accelerate segmental bone healing. In this study, we explored whether FLP/Frt-hybrid baculovirus vector engineered rabbit MSC are able to assist and accelerate segmental calvarial bone healing. Within the BMSCs transduced with Bac-FLP and Bac-FCOEE, all subsequent transductions were performed at MOI 100/100 at an interval of 4 h and no obvious anti-virus reaction, enabling transgene persistence in episomal form and prolonging the expression to >28 days. BMSCs engineered by the conventional baculovirus transiently expressing BMP2/VEGF (S group) only healed the critical size (8 mm) segmental calvarial bone defects in 20 % of New Zealand White rabbits at 12 weekspost-implantation, whereas BMSCs engineered by the hybrid vectors persistently expressing BMP2/VEGF (L group) healed the critical-size defects in 87 % in 8 weeks. Compared with the S group, the L group can accelerated the healing