Purpose: Osteoradionecrosis (ORN) of the mandible is a serious complication of radiation therapy, and accompanies soft tissue damage before bone loss appears. However, there is still no adequate treatment to heal the soft tissue damage of ORN. This study investigated the effect of platelet-derived growth factor (PDGF) or rat mesenchymal stem cells (rMSCs) on the healing of radiation-induced soft tissue injury by varying administration timing.
Methods: Rats were bilaterally irradiated in both right and the left flanks at a dose of 50 Gy. Experimental groups were randomly divided into three groups, and received PDGF (8 μg), rMSCs (106 cells) or PDGF+rMSCs in left side next day (Group 1) or at three weeks (Group 2) after irradiation, while the right side each was used as vehicle control. Each wound was analyzed by defining the percentage of ulcerated area to the irradiated during five weeks healing period after administration of PDGF or rMSCs, and histological observation.
Results: Greater than 60% of skin within each irradiated zone underwent ulceration within 16 days after irradiation, and reached peak ulceration above 50% around 3 weeks after irradiation. There was no any improvement of wound healing in all treatments of Group 1. However, the combined treatment of PDGF and rMSCs of Group 2 significantly reduced the wound size by 50.5%, compared to non-treated control while either rMSCs or PDGF alone of Group 2 showed no significant healing effect. PDGF treatment (PDGF alone or PDGF and rMSCs mixes) of Group 2 exhibited highly organized collagen fiber deposition in full-thickness, compared with vehicle control.
Conclusions: These results suggest that the combined administration of MSCs and PDGF efficiently enhanced the healing of radiation-induced skin ulceration when administered at time point when ulceration reaches peak in comparison with non-effect with immediate injection after irradiation.
17 May 2014 - 20 May 2014