Human blood-derived endothelial progenitor cells augment vasculogenesis and osteogenesis.

Abstract

Endothelial progenitor cells (EPC) participate in angiogenesis andosteogenesis, therefore, have the potential to enhance extra-cortical bone formation. To enhance extra-cortical bone formation following local transplantation of human peripheral blood-derived EPC (hEPC) in a guided bone regeneration (GBR) nude rat calvaria model. hEPC were isolated from peripheral blood of healthy volunteers. Cells were cultured and characterized by flow cytometry for specific endothelial markers. Following exposure of nude rat calvaria, gold domes were filled with 10(6) hEPC mixed with βTCP (n=6). Domes filled with βTCP served as control (n=6). Rats were sacrificed after 3months. New bone formation and blood vessel density were analysed by histology and histomorphometry. Transplanted hEPC were located in the regenerated tissue using immunohistology. Abundant vasculature was observed adjacent to the newly formed bone. According to histomorphometric analysis: blood vessel density was 7.5 folds higher in the hEPC compared with the control group. Similarly, gained extra-cortical bone height (2.46±1.1mm versus 0.843±0.61mm, p=0.01) and bone area fraction (19.42±7.48% versus 4.81±3.93%, p=0.001) were elevated following hEPC transplantation. Moreover, hEPC expressing human-specific CD31 were integrated into blood vessel walls adjacent to newly formed bone. In nude rat GBR calvaria model, transplantation of hEPC significantly enhanced vasculogenesis and osteogenesis.