Abstract
A significant number of fractures develop non-union. Stem cell therapy may be beneficial in their treatment, however this requires acquisition, culture and delivery of stem cells. Stem cell homing and migration is regulated through SDF-1 and its receptor CXCR4. Studies have demonstrated endogenous mobilisation of different populations of stem and progenitor cells by administering growth factors with a pharmacological antagonist of CXCR4, AMD3100. This may therefore be a means to improve compromised fracture healing. A 1.5mm femoral osteotomy in adult female Wistar rats was stabilised with an external skeletal fixator. After osteotomy, saline/PBS (P) VEGF (V), IGF-1 (I) or GCSF (G) (100ug/kg, 0.5ml/100g i.p.), were administered daily for 4 days. On day 5, a single 5mg/kg i.p. dose of AMD3100 was given. Control group (C) did not receive growth factors or AMD 3100. At 5 weeks, the femur was retrieved and microCT scanned. Compared to group C (n=7), group P (n=5) had a significant increase in bone volume (P=0.01) 8.9±2.2um∧3 (control 4.3±3.1um∧3) and trabecular thickness (P=0.03). Group I (n=6) also had a significant increase in bone volume (P=0.035) 5.1±4.2um∧3 and trabecular thickness 0.062±0.008um (control 0.042±0.01um) (P=0.01). Group V (n=8), showed a non-significant increase in bone volume; 5.22±1.7um∧3 and trabecular thickness 0.048±0.007um. Group G (n=5) showed a significant decrease in bone volume (2.5±2.6um∧3) (P=0.048). AMD3100 alone and IgF1-AMD3100, showed the greatest increase in bone formation, presumably through mobilisation of beneficial combinations of stem and progenitor cells. GCSF-AMD3100, which is expected to mobilise hematopoietic progenitors inhibited bone healing.
