BFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis in rabbits

Abstract

Distraction osteogenesis (DO), which induces new bone formation along the vector of pull without requiring the use of bone graft, has become a valuable surgical method for patients with limb discrepancy or craniofacial microsomia. However, the long treatment period and possible fibrous union or nonunion hampers its further clinical application. Bone marrow mesenchymal stem cells (BMMSCs) have been widely used as a source of cell therapy or a vector for gene transfer. Basic fibroblast growth factor (bFGF) has high potential for promotion of bone regeneration. However, bFGF has a short half value period in vivo. In this study, osteodistraction was applied in craniofacial bone of rabbit to observe the effects of BMMSCs with or without bFGF gene transfected on bone regeneration in the distracted zone. Mandibular lengthening (10 mm) was performed in 42 New Zealand white rabbits using a rapid distraction rate (2 mm/day). The animals were then randomly divided into group A, group B and group C ( n = 14 for each group). At the end of distraction, physiological saline, autologous BMMSCs and BMMSCs transfected with bFGF were injected into the distraction gaps in groups A, B, and C, respectively. Eight weeks after DO, the rabbits were sacrificed, and the distracted mandibles were harvested and processed for radiography, dual energy x-ray absorptiometry (DXA), micro-CT, histology and three-point bend testing. Under a rapid distraction, immature or poor bone healing was observed in the distracted callus from group A. However, better bone formation and higher bone mineral density (BMD) and bone mineral content (BMC) in the distracted callus were observed in group B and group C, the latter showed excellent bone formation and highest BMD and BMC. Such finding was confirmed by histological and micro-CT examinations. The values of BT/TV in group C were highest and the micro-architecture presented more mature characteristics. The mechanical strength in group C was 1.63-fold and 1.28-fold greater than that in group A and B by three-point bending testing. The results of this study suggest that BMMSCs transplantation can promote bone formation in DO, and bFGF-modified BMMSCs were more effective in this enhancement.