Wang L, Zhao Y, Cao J, Yang X, Lei D
State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China.
Department of Prosthodontics, Stomatology Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Br J Oral Maxillofac Surg. 2015 Mar;53(3):279-84. doi: 10.1016/j.bjoms.2014.12.014. Epub 2015 Jan 15.
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.
牵张成骨术广泛应用于治疗骨畸形和骨缺损。然而，下牙槽神经损伤是一个令人担忧的问题。我们的目的是研究在兔下颌骨牵张成骨术中使用慢病毒介导的人β神经生长因子（hNGFβ）治疗下牙槽神经的可行性。为此，从兔下颌骨骨髓中分离间充质干细胞（MSC），并使用含有hNGFβ的重组慢病毒载体对其进行基因工程改造。20只新西兰白兔接受下颌骨牵张成骨术，将500万个经hNGFβ载体或对照载体转导的MSC移植到手术中骨骨折间隙处的神经周围（每组n = 10）。逐渐牵张后，采集神经样本进行组织学和组织形态计量学分析。我们发现，通过ELISA检测，慢病毒载体转导的基因工程化MSC能够分泌生理相关浓度的hNGFβ。神经组织学检查显示，植入hNGFβ修饰的MSC的组比对照组有更多的再生神经纤维和更少的髓磷脂碎片。神经组织形态计量学分析显示，植入hNGFβ修饰的MSC的组比对照组有更高的有髓纤维密度。数据表明，植入hNGFβ修饰的MSC可以加速兔下颌骨牵张成骨术中下牙槽神经的形态恢复。利用慢病毒介导的基因治疗通过MSC递送hNGFβ可能是一种将神经损伤降至最低的有前景的方法。
