BMP-2-transduced human bone marrow stem cells enhance neo-bone formation in a rat critical-sized femur defect

Abstract

Synthetic graft materials are considered as possible substitutes for cancellous bone, but lack osteogenic and osteoinductive properties. In this study, we investigated how composite scaffolds of βTCP containing osteogenic human bone marrow mesenchymal stem cells (hBMSCs) and osteoinductive bone morphogenetic protein-2 (BMP-2) influenced the process of fracture healing. hBMSCs were loaded into βTCP scaffolds 24 h before implantation in a rat critical-sized bone defect. hBMSCs were either stimulated with rhBMP-2 or transduced with BMP-2 by gene transfer. The effect of both protein stimulation and gene transfer was compared for osteogenic outcome. X-rays were conducted at weeks 0, 1, 3, 6, 9 and 12 post-operatively. In addition, bone-labelling fluorochromes were applied at 0, 3, 6 and 9 weeks. Histological analysis was performed for the amount of callus tissue and cartilage formation. At 6 weeks, the critical-sized defect in 33% of the rats treated with the Ad-BMP-2-transduced hBMSCs/βTCP scaffolds was radiographically bridged. In contrast, in only 10% of the rats treated with rhBMP2/hBMSCs, 12 weeks post-treatment, the bone defect was closed in all treated rats of the Ad-BMP-2 group except for one. Histology showed significantly higher amounts of callus formation in both Ad-BMP-2- and rhBMP-2-treated rats. The amount of neocartilage was less pronounced in both BMP-2-related groups. In summary, scaffolds with BMP-2-transduced hBMSCs performed better than those with the rhBMP2/hBMSCs protein. These results suggest that combinations of osteoconductive biomaterials with genetically modified MSCs capable of secreting osteoinductive proteins may represent a promising alternative for bone regeneration. Copyright © 2015 John Wiley & Sons, Ltd.

Keywords: adenovirus; bone marrow stem cells; bone morphogenetic protein 2; femur critical-sized bone defect; gene transfer; rat.