Differential Effects of Vascular Endothelial Growth Factor on Bone Regeneration of Human Adipose Tissue-Derived Mesenchymal Stem Cells and Bone Marrow Mesenchymal Stem Cells

Human adipose tissue-derived stromal cells (ATSCs) and human bone marrow stromal cells (BMSCs) are promising stem cell sources for bone regeneration. However, implantation of ATSCs or BMSCs alone induces partial effect on bone formation. Angiogenesis and blood supply are essential in tissue survival after implantation. We investigated effects of vascular endothelial growth factor (VEGF), a well known angiogenic factor, on ATSC- and BMSC-induced bone regeneration. In vitro effects of VEGF on the proliferation (MTS assay) and osteogenic differentiation (ALP and Alizarin Red staining) of ATSCs and BMSCs were examined. ATSCs and BMSCs were seeded on biphasic calcium phosphate (BCP), treated with VEGF, and implanted on calvarial defects of nude mice. Bone regeneration was assessed by Micro-CT and histology at 10 weeks after implantation. Proliferation and differentiation of ATSCs and BMSCs was not increased by VEGF in vitro. However, BMSCs and ATSCs treated with VEGF showed increased bone mineral density (BMD) and bone mineral content (BMC) as assessed by micro-CT. In addition, histomorphometric analysis showed that new bone formation was significantly increased in VEGF-treated ATSCs (30%) and BMSCs (21%) groups compared to untreated group. These results demonstrated that adult MSCs (ATSCs and BMSCs) treated with VEGF can promote bone regeneration in calvarial critical-sized defect model. Taken together, VEGF can be a useful factor for bone repair and regeneration.