Autologous bone grafts with MSCs or FGF-2 accelerate bone union in large bone defects

Hiroaki Murakami, Tomoyuki Nakasa, Masakazu Ishikawa, Nobuo Adachi, Mitsuo Ochi

Although the contribution of fibroblast growth factor (FGF)-2 and mesenchymal stromal cells (MSCs) to bone formation is well known, few studies have investigated the combination of an autologous bone graft with FGF-2 or MSCs for large bone defects. We studied an atrophic non-union model with a large bone defect, created by resecting a 10-mm section from the center of each femoral shaft of 12-week-old Sprague-Dawley rats. The periosteum of the proximal and distal ends of the femur was cauterized circumferentially, and excised portions were used in the contralateral femur as autologous bone grafts. The rats were randomized to three groups and given no further treatment (group A), administered FGF-2 at 20 μg/20 μL (group B), or 1.0 × 10(6) MSCs (group C). Radiographs were taken every 2 weeks up to 12 weeks, with CT performed at 12 weeks. Harvested femurs were stained with toluidine blue and evaluated using radiographic and histology scores. Radiographic and histological evaluation showed that bone union had been achieved at 12 weeks in group C, while group B showed callus formation and bridging callus but non-union, and in group A, callus formation alone was evident. Both radiographic and histological scores were significantly higher at 2, 4, 6, 8, 10, and 12 weeks in groups B and C than group A and also significantly higher in group C than group B at 12 weeks. These data suggest that autologous bone grafts in combination with MSCs benefit difficult cases which cannot be treated with autologous bone grafts alone.