Effect of bone marrow-derived stem cells and bone morphogenetic protein-2 on treatment of osteoradionecrosis in a rat model

Abstract

We investigated the effect of rat mesenchymal stem cells (rMSCs) and bone morphogenetic protein-2 (BMP-2) on the osseous healing of osteoradionecrosis in the rat mandible, depending on application time. One week after irradiation (30 Gy) on the right mandible, all molar teeth were extracted. In Group 1 (n = 25), rMSCs and/or BMP-2 carried with hydrogel were applied immediately after surgery. In Group 2 (n = 25), application was done 4 weeks after surgery, after the occurrence of osteoradionecrosis. No hydrogel (n = 5), hydrogel alone (n = 5), hydrogel with 2 × 10(4) rMSCs (n = 5), hydrogel with 10 μg of BMP-2 (n = 5), or hydrogel with 10 μg of BMP-2 and 2 × 10(4) rMSCs (n = 5) was applied. Micro-CT data of bone healing were collected at 4 weeks post-application. In Group 1, BMP-2 was effective in increasing both bone volume (BV) and bone mineral density (BMD), whereas rMSCs were not. In Group 2, the combined application of rMSCs and BMP-2 significantly increased BMD and BV compared to values in the groups without hydrogel and with hydrogel alone. Osseous healing after post-irradiation trauma in rats was enhanced immediately after dentoalveolar trauma by application of BMP-2, whereas the combined application of rMSCs and BMP-2 was most effective after osteoradionecrosis occurred.