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

Abstract

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/-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. Copyright (c) 2017 John Wiley & Sons, Ltd.