BoneKEy Reports | BoneKEy Watch
Bone healing augmented by experimentally induced MSC mobilization
DOI:10.1038/bonekey.2012.167
Using a model in which mice with an induced segmental defect were injected with different growth factors, Kumar et al. sought to determine whether it was possible to mobilize mesenchymal stem cells (MSC) in vivo to augment bone growth and repair. Injection of either IGF1, PDGF, SCF or VEGF followed by CXCR4 antagonist AMD3100 all resulted in larger numbers of colony-forming MSC in the mice's blood, with the greatest response seen with IGF1.
Follow-up experiments revealed that IGF1 plus AMD3100 augmented bone growth in the model, as shown by results obtained from histomorphometry, DXA scans and micro-CT scans.
Mobilization of the MSC after treatment was due to increased proliferation and migration, and resulted in elevated levels of key factors in several major signaling pathways, including Smad2/3, P13K/Akt and MEK1/2-Erk1/2. Levels of EGFR, cadherin and p70 were measured but remained static, indicating that pathways in which those factors act were not involved.
Editor's comment: The observed therapeutic effects of IGF1 in combination with the CXCR4 antagonist, AMD3100, may have been influenced through improved neovasculogenesis/angiogenesis around the fracture site from mobilization of hematopoietic stem cells and endothelial progenitor cells and their homing to the fracture site. Follow-up studies to verify the long-term fate of mobilized MSC are needed to assess prospects of clinical application.
Subject terms: Fracture repair; extracellular signaling molecules; bone remodeling.
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