hBMP-2 and hTGF-β1 expressed in implanted BMSCs synergistically promote the repairing of segmental bone defects.

Abstract

To evaluate the effects of co-expressing hBMP-2 and hTGF-β1 in BMSCs (bone marrow-derived mesenchymal stem cells) on the repairing process of radial segmental defects in rats. BMSCs were infected with a high titer recombinant adenovirus carrying hTGF-βl and/or hBMP-2 genes. Expression of exogenous genes in BMSCs was confirmed by RT-PCR and ELISA assays. In vitro effects of exogenous genes were assessed by MTT and ALP activity tests. A left radial defect model was created using 120 SD rats. Genetically modified or unmodified BMSCs were implanted with collagen sponge scaffolds into the 5-mm radial defect. The bone repair process was systematically monitored and evaluated by X-ray examinations, gross anatomic examinations, histological analyses, and biomechanical tests. Expression of hBMP-2 and hTGF-β1 showed synergistic effects on promoting BMSC proliferation and enhancing ALP activity in vitro. Bone repair assays showed that hBMP-2 and hTGF-β1 promoted the production of chondrocytes and osteoblasts. Implanted BMSCs transfected with both hBMP-2 and hTGF-β1 led to the best bone repair outcome. hBMP-2 and hTGF-β1 can synergistically improve the bone repair process. Our results suggest a potential clinical value of combining hBMP-2 and hTGF-β1 in repairing bone defects.