Systemic Injection of Substance P Promotes Murine Calvarial Repair Through Mobilizing Endogenous Mesenchymal Stem Cells.

Craniofacial defect is a critical problem in dental clinic, which has a tremendous impact on patients' quality of life. Mesenchymal stem cell-based therapy has emerged as a promising approach for tissue defect repair. However, reduced survival after mesenchymal stem cells (MSCs) transplantation remains as a major problem in this area, which hampers the outcome of regeneration. Recently, the mechanism to mobilize endogenous MSCs for tissue regeneration has received increasing attentions, as it does not require exogenous cell transplantation. The primary goal of this study was to confirm the role of intravenous substance P in mobilizing endogenous CD45 ^- CD11b ^- CD29 ⁺ MSCs in critical-sized bone defect animals and to investigate the effects of substance P on calvarial bone repair. Flow cytometry analyses revealed that intravenous substance P promoted the mobilization of endogenous CD45 ^- CD11b ^- CD29 ⁺ MSCs after bone defect. In addition, Micro-CT showed that intravenous substance P improved the outcomes of calvarial bone repair. Furthermore, we discovered that systemic injection of substance P attenuated inflammation and enhanced the survival of the local-transplanted GFP ⁺ MSCs. Our findings suggested that substance P together with its mobilized CD45 ^- CD11b ^- CD29 ⁺ MSCs helped improve calvarial defect repair through regulating inflammatory conditions and promoting the survival of local-transplanted cells.