Vascular endothelial growth factor-transfected adipose-derived stromal cells enhance bone regeneration and neovascularization from bone marrow stromal cells

Vascular endothelial growth factor (VEGF)-transfected adipose-derived stromal cells (ADSCs^VEGF) were devised to promote bone regeneration and neovascularization of bone marrow stromal cells (BMSCs). ADSCs^VEGF were added to BMSCs and cocultured in variable proportions. ADSCs^VEGF alone or ADSCs^VEGF with BMSCs (BMSCs:ADSCs^VEGF ratio of 1:0.025–0.5) induced significantly greater tube formation in human umbilical vein endothelial cells than untransfected ADSCs. The cocultures of BMSCs and ADSCs^VEGF at ratios of 1: 0.025–0.1 showed significantly greater osteogenic differentiation and mineralization than BMSCs alone in vitro. Osteogenic markers COL1A1, OCN and BSP were most effectively induced at the BMSC: ADSC^VEGF ratio of 1:0.05. Of angiogenesis-related genes, upregulation of cathepsin Z and downregulation of early growth response 1 were observed while two osteogenesis-related genes, osteoactivin and tetranectin, were upregulated in BMSCs/ADSCs^VEGF compared to BMSCs/ADSCs. When critical size calvarial defects in rats were implanted with mixture of BMSCs and ADSCs^VEGF along with hydroxyapatite/β-tricalcium phosphate granules, BMSCs and ADSCs^VEGF at the ratio of 1:0.05 showed better bone regeneration that BMSCs alone. The cotransplantation of ADSCs^VEGF with BMSCs significantly increased neovascularization on the regenerated bone of the repaired defect than BMSCs alone. In conclusion, ADSCs^VEGF added in small proportion to BMSCs effectively promote bone regeneration and neovascularization.