Mesenchymal stem cells modified with nerve growth factor improve recovery of the inferior alveolar nerve after mandibular distraction osteogenesis in rabbits.
Distraction osteogenesis is widely used in the treatment of bony deformities and defects. However, injury to the inferior alveolar nerve is a concern. Our aim was to investigate the feasibility of using lentiviral-mediated human nerve growth factor beta (hNGFβ) of the inferior alveolar nerve in mandibular distraction osteogenesis in rabbits. To achieve this, mesenchymal stem cells (MSC) from the bone marrow of rabbit mandibles were isolated and genetically engineered using recombinant lentiviral vector containing hNGFβ. Twenty New Zealand white rabbits underwent mandibular distraction osteogenesis, and 5 million MSC transduced with hNGFβ-vector or control vector were transplanted around the nerve in the gap where the bone had been fractured during the operation (n=10 in each group). After gradual distraction, samples of the nerve were harvested for histological and histomorphometric analysis. We found that the genetically engineered MSC transduced by the lentiviral vector were able to secrete hNGFβ at physiologically relevant concentrations as measured by ELISA. Histological examination of the nerve showed more regenerating nerve fibres and less myelin debris in the group in which hNGFβ-modified MSC had been implanted than in the control group. Histomorphometric analysis of the nerve showed increased density of myelinated fibres in the group in which hNGFβ-modified MSC had been implanted than in the control group. The data suggest that implantation of hNGFβ-modified MSC can accelerate the morphological recovery of the inferior alveolar nerve during mandibular distraction osteogenesis in rabbits. The use of lentiviral-mediated gene treatment to deliver hNGFβ through MSC may be a promising way of minimising injury to the nerve.
['Wang|L|L|', 'Zhao|Y|Y|', 'Cao|J|J|', 'Yang|X|X|', 'Lei|D|D|']
D000818:Animals D005240:Feasibility Studies D005822:Genetic Vectors D006801:Humans D016086:Lentivirus D008297:Male D008334:Mandible D008340:Mandibular Nerve D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D009186:Myelin Sheath D009412:Nerve Fibers D009413:Nerve Fibers, Myelinated D020932:Nerve Growth Factor D009416:Nerve Regeneration D019857:Osteogenesis, Distraction D010957:Plasmids D011817:Rabbits D011897:Random Allocation D020127:Recovery of Function D014161:Transduction, Genetic D014945:Wound Healing
Nerve growth factor Distraction osteogenesis Rabbit Bone marrow mesenchymal stem cells Gene therapy Nerve injury