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 (ADSCsVEGF ) were devised to promote bone regeneration and neovascularization of bone marrow stromal cells (BMSCs). ADSCsVEGF were added to BMSCs and cocultured in variable proportions. ADSCsVEGF alone or ADSCsVEGF with BMSCs (BMSCs:ADSCsVEGF 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 ADSCsVEGF 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: ADSCVEGF 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/ADSCsVEGF compared to BMSCs/ADSCs. When critical size calvarial defects in rats were implanted with mixture of BMSCs and ADSCsVEGF along with hydroxyapatite/β-tricalcium phosphate granules, BMSCs and ADSCsVEGF at the ratio of 1:0.05 showed better bone regeneration that BMSCs alone. The cotransplantation of ADSCsVEGF with BMSCs significantly increased neovascularization on the regenerated bone of the repaired defect than BMSCs alone. In conclusion, ADSCsVEGF added in small proportion to BMSCs effectively promote bone regeneration and neovascularization.