The optimal time to inject bone mesenchymal stem cells for fracture healing in a murine model

• DOI: 10.1186/s13287-018-1034-7
• Publication Date: 2018-10-25T09:02:07Z
• Authors: Xin Wang; Cheng Wang; Wenlong Gou; Xiaolong Xu; Yu Wang; Aiyuan Wang; Wenjing Xu; Quanyi Guo; Shuyun Liu; Qiang Lu; Haoye Meng; Mei Yuan; Jiang Peng; Shibi Lu
• Keywords: Male; Medicine (General); Benzylamines; Bone Regeneration; Homing; Gene Expression; Fracture healing; QD415-436; Cyclams; Mesenchymal Stem Cell Transplantation; Biochemistry; Stromal cell-derived factor 1; Mice; 03 medical and health sciences; R5-920; Bone Density; Heterocyclic Compounds; Osteogenesis; Animals; Femur; Cell Engineering; Migration; Fracture Healing; 0303 health sciences; Research; Mesenchymal Stem Cells; Chemokine CXCL12; Mice, Inbred C57BL; Disease Models, Animal; Luminescent Proteins; Mesenchymal stem cells; Femoral Fractures

Bone marrow is an important source of stem cells, which can promote bone fracture healing.We investigated the optimal time to inject bone marrow mesenchymal stem cells (BMSCs) in a C57 murine unilateral, transverse, femur fracture model. BMSCs transfected with red fluorescent protein (RFP-BMSCs) were injected via the tail vein on day 1, 7, or 14 post-fracture. AMD3100 (inhibitor of stromal cell-derived factor 1 [SDF-1]) was also injected before RFP-BMSCs in one group for comparison; a control group received saline injections. RFP-BMSC migration and fracture healing were evaluated by in vivo fluorescence assay. Micro-CT was performed and mechanical testing and histological analysis. Chemokine levels were evaluated by quantitative real-time PCR and western blotting.Following injection on day 7 post-fracture, RFP-BMSCs more frequently homed to the fracture site and remained for a longer duration. Bone volume and bone mineral density were increased when BMSCs were injected on day 7 post-fracture (P < 0.05). The mechanical properties of fractured femurs were improved following day-7 BMSC injection. Histology confirmed that BMSC injection improved the formation of new bones.Chemokines that induce BMSC migration were highly expressed, and protein levels of osteogenesis-related factors were increased. Seven days after fracture may be the optimal time for injection of BMSCs to promote fracture healing. Additionally, the SDF-1/CXCR4 pathway may play an important role in fracture healing following BMSC injection.