Enhancement of human peripheral blood mononuclear cell transplantation-mediated bone formation

Recent studies have demonstrated the existence of osteoblast progenitor cells in circulating blood. Here we show that local delivery of bone morphogenetic protein-2 (BMP-2) to cell transplantation sites induces in situ osteogenic differentiation of transplanted human peripheral blood mononuclear cells (PBMNCs) and enhances in vivo bone formation mediated by PBMNC transplantation. Human PBMNCs were seeded on scaffolds with or without BMP-2 and implanted subcutaneously into athymic mice. Nonseeded scaffolds with BMP-2 were also implanted. Eight weeks later, radiographic and histological analyses showed that the PBMNC + BMP-2 group had undergone much more extensive bone formation than either the PBMNC group or BMP-2 group. Only the PBMNC + BMP-2 group expressed human Cbfa1, osteonectin, and osteocalcin, suggesting in situ osteogenic differentiation of and bone formation by transplanted human PBMNCs, while the other groups did not express these genes. This study provides a method to enhance human PBMNC transplantation-mediated bone formation.