Endothelial progenitor cells with stem cells enhance osteogenic efficacy.

Background: Mesenchymal stem cell (MSC)-based bone tissue engineering is a promising treatment option for maxillary sinus augmentation. Rapid vascularization is necessary to enhance the osteoinductive efficacy and prevent necrosis of the tissue-engineered bone. This study investigated whether the co-autotransplantation of endothelial progenitor cells (EPCs) could significantly enhance the in vivo osteogenic efficacy of MSCs and prevent necrosis of the tissue-engineered bone in a maxillary sinus augmentation model in dogs. Methods: We evaluated the in vitro osteogenic activities of a clinically-used scaffold-deproteinized bovine bone (Bio-Oss) by examining cell adhesion and alkaline phosphatase (ALP) activity. In vivo, sinus augmentations were performed identically on both sides of dogs (n = 3 per group) using three treatment groups: (A) Bio-Oss with MSCs and EPCs; (B) Bio-Oss with MSCs; and (C) Bio-Oss with EPCs. The tissue implants were evaluated 24 weeks post-implantation. Results: In vitro, co-application of EPCs and MSCs on Bio-Oss significantly enhanced adhesion and ALP activity. In vivo, coautotransplantation of MSCs and EPCs resulted in a significantly higher height, compressive strength, bone volume density, trabecular thickness, and trabecular number and a significantly lower trabecular separation compared with the other groups. The fluorescent test showed co-autotransplantation caused a significantly higher mineral apposition rate than the other groups. Histomorphometric analysis showed co-application resulted in the highest rate of new bone formation. Newly formed bone was frequently in the center of the implants with EPCs and MSCs, but not the other implants. Conclusions: Co-autotransplantation of EPCs and MSCs significantly enhanced the in vivo osteogenic efficacy, suggesting promising potential for sinus augmentation.