Mesenchymal stem cells modified with nerve growth factor improve recovery of the inferior alveolar nerve after mandibular distraction osteogenesis in rabbits
Mesenchymal stem cells modified with nerve growth factor improve recovery of the inferior alveolar nerve after mandibular distraction osteogenesis in rabbits
复制标题
神经生长因子修饰的间充质干细胞改善兔下颌骨牵张成骨后下牙槽神经的恢复
DOI：
10.1016/j.bjoms.2014.12.014
复制
发表时间：
2015-03-01
影响因子：
1.8
通讯作者：
Lei, D.
中科院分区：
文献类型：
--
作者：
Wang, L.;Zhao, Y.;Lei, D.
牵张成骨术广泛应用于骨畸形和骨缺损的治疗。然而，下牙槽神经的损伤是一个问题。我们的目的是探讨使用慢病毒介导的人神经生长因子β（hNGF β）的下牙槽神经在兔下颌骨牵张成骨的可行性。为了实现这一目标，从兔下颌骨骨髓中分离间充质干细胞（MSC），并使用含有hNGF β的重组慢病毒载体进行基因工程改造。20只新西兰白色兔行下颌骨牵张成骨术，将500万只转染hNGF β-载体或对照载体的MSC移植到术中骨折处差距的神经周围（每组n = 10）。逐渐牵张后，收集神经样本进行组织学和组织形态计量学分析。我们发现，通过慢病毒载体转导的基因工程MSC能够分泌生理相关浓度的hNGF β，如通过ELISA测量的。神经的组织学检查显示，与对照组相比，hNGF β修饰的MSC植入组中再生的神经纤维更多，髓鞘碎片更少。神经的组织形态学分析显示，hNGF β修饰的MSC植入组中有髓纤维的密度比对照组增加。实验结果表明，hNGF β修饰的MSC植入兔下颌骨牵张成骨过程中，可促进下牙槽神经的形态学恢复。使用慢病毒介导的基因治疗通过MSC递送hNGF β可能是最小化神经损伤的有希望的方法。(C)2015年英国口腔颌面外科医师协会。由爱思唯尔有限公司出版。保留所有权利。
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 (hNGF beta) 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 hNGF beta. Twenty New Zealand white rabbits underwent mandibular distraction osteogenesis, and 5 million MSC transduced with hNGF beta-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 hNGF beta 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 hNGF beta-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 hNGF beta modified MSC had been implanted than in the control group. The data suggest that implantation of hNGF beta-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 hNGF beta through MSC may be a promising way of minimising injury to the nerve. (C) 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.