Abstract
BackgroundBone marrow is an important source of stem cells, which can promote bone fracture healing.MethodsWe 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.ResultsFollowing 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.ConclusionsChemokines 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.
Highlights
Bone marrow is an important source of stem cells, which can promote bone fracture healing
The presence of C-X-C chemokine receptor type 4 (CXCR4) is essential for Mesenchymal stem cells (MSCs) homing to the fracture site To assess MSC homing at the femur fracture site, we injected RFP-transfected bone-marrow MSCs (BMSCs) (RFP-BMSCs) into mice on days 1, 7, and 14 post-fracture
In fluorescence imaging analysis, following a day-1 injection, RFP signal intensity was greater on days 7 and 14 when RFP-BMSCs were injected in the absence of AMD3100, signal intensity was similar in both groups on day 28
Summary
Bone marrow is an important source of stem cells, which can promote bone fracture healing. Delayed bone union can lead to non-union and severe dysfunction and is difficult to treat [1]. Mesenchymal stem cells (MSCs) are nonhematopoietic stromal stem cells that exhibit multipotent differentiation into chondrocytes and osteocytes [2]. Homing of MSCs may play an important role in the repair of bone fractures. Bone marrow is an important source of stem cells. Many studies have investigated the use of bone-marrow MSCs (BMSCs) therapy to promote fracture healing.
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