Recombinant human bone morphogenetic protein-2 potentiates the in vivo osteogenic ability of marrow/hydroxyapatite composites

A composite of marrow mesenchymal stem cells (MSCs) and porous hydroxyapati te (HA) has bone-forming capability. To promote the capability, we added re combinant human bone morphogenetic protein-2 (BMP) to the composite. The bo ne formation was assessed by rat subcutaneous implantation of 4 different k inds of implants, i.e., HA alone, BMP/HA composites, MSCs/HA composites, an d the composites containing BMP (MSCs/ BMP/HA). Both HA and the BMP/HA comp osites did not show bone formation at any time after implantation. The MSCs /HA composites showed moderate bone formation at 4 weeks and extensive bone formation at 8 weeks. The MSCs/BMP/HA composites showed obvious bone forma tion together with active osteoblasts at 2 weeks and more bone formation at 4 and 8 weeks. The MSCs/BMP/ HA composites demonstrated high alkaline phos phatase and osteocalcin expression at both the protein and gene levels. The se results indicate that the combination of MSCs, porous HA, and BMP synerg istically enhances osteogenic potential and provides a rational basis for t heir clinical application in bone reconstruction surgery.