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Distraction osteogenesis (DO) is one of the most promising reconstructive methods for repairing large craniofacial defects or growth deficiencies through bone regeneration, but it is also a challenge because of an undesirably long process and its complications, which limit its application in clinical practice. The transplantation of mesenchymal stem cells (MSCs) is regarded as an innovative approach to accelerate bone regeneration. Dental pulp stem cells (DPSCs) have shown some advantages over other human adult MSCs, and DPSCs have been regarded as one of the most promising cell sources used in the endogenous tissue engineering. Furthermore, using stem cells modified by gene engineering in DO has been reported in previous studies. It has been shown that Sirtuin-1 (SIRT1) can directly regulate the differentiation of MSCs into osteoblasts. In this study, DPSCs expressing SIRT1 were prepared and their effects on the new bone formation were further investigated in rabbits with tibia. Rabbits were injected with the adenovirus (Adv)-SIRT1-green fluorescent protein (GFP)-transfected DPSCs (overexpression group, Group OE), Adv-GFP transfected DPSCs (negative control group, Group NC) or physiologic saline (control group, Groups CON) into the distraction gap. The new bone tissues in the distraction gap were harvested 8 weeks later, and subjected to by radiographic examination, micro-CT evaluation, and histological and mechanical testing. The better bone formation, the highest bone mineral density (BMD) and the highest bone mineral content (BMC) were observed in the OE group. In conclusion, SIRT1-modified DPSCs in DO was more effective to promote new bone formation during DO, which provides evidence for further investigation about the role of of SIRT1 in the DO., Competing Interests: None.

Objective: This work investigated mesenchymal stem cells (MSCs) modified with Runt-related transcription factor 2 (Runx2) therapy for bone regeneration in rabbit mandibular distraction osteogenesis., Methods: Forty-eight New Zealand mature white rabbits were randomly divided into three groups after the rabbit model of mandibular distraction osteogenesis was established: reconstruction plasmid modified with Runx2 (group A), plasmid without Runx2 (group B), and the same dose of saline as control (group C). At the fifth day of distraction phase, MSCs with reconstruction plasmid modified with adv-hRunx2-gfp were injected into the distraction gap of group A. MSCs with reconstruction plasmid modified with adv-gfp was injected into the distraction gap of group B, whereas group C was injected with the same dose of saline. At 8 weeks after injection, all animals were sacrificed, and the distracted mandibles were harvested. The general imaging histological observation and three-point bending test were used for evaluation., Results: CT plain scan and histological analysis confirmed that the amount of new bone forming in the distraction gap of group A was significantly higher than those in groups B and C. Dual-energy X ray and three-point bending test results also showed that the bone mineral density, bone mineral content, and maximum load of the distraction gap of group A were significantly higher than those of groups B and C (P<0.01)., Conclusion: Runx2-ex vivo gene therapy based on MSCs can effectively promote the bone regeneration in rabbit mandibular distraction osteogenesis and shorten the stationary phase. Therefore, reconstruction of craniofacial fracture would be a valuable strategy