Chen Y-L, Chen P K-T, Jeng L-B, Huang C-S, Yang L-C, Chung H-Y, Chang S C-N
Department of Dentistry, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan.
Gene Ther. 2008 Nov;15(22):1469-77. doi: 10.1038/gt.2008.131. Epub 2008 Aug 14.
The regeneration of the periodontal attachment apparatus remains clinically challenging because of the involvement of three tissue types and the complexity of their relationship. Human recombinant bone morphogenic protein-2 (rhBMP-2) can accelerate the regeneration of bone and cementum and the insertion of periodontal ligament fibers but may lead to a deranged periodontal relationship, ankylosis and root resorption.This study evaluated a novel approach to regeneration of the periodontal attachment apparatus using a combination of ex vivo autologous bone marrow mesenchymal stem cells (MSCs) engineered by replication-defective adenovirus to express the BMP-2 gene and Pluronic F127 (PF127). Twenty-four periodontal defects were surgically created in 12 New Zealand white rabbits and randomly assigned to three experimental groups with MSCs: the advBMP-2 group; the advbetagal group; the MSC group and one control group: PF127 only. The regenerated periodontal attachment apparatus was assessed histologically and the total regenerated bone volume was calculated from three-dimensional computed tomography analysis.This approach regenerated not only cementum with Sharpey's fiber insertion, but also statistically significant quantities of bone, re-establishing a more normal relationship among the components of the regenerated periodontal attachment apparatus, which is beneficial for the maintenance of periodontal health.Ex vivo gene transfer using stem cells as vectors may provide an advantage of slower BMP-2 release, increasing cementogenesis. There is regeneration of the periodontal attachment apparatus, whereas direct usage of the protein (rhBMP-2) yields unhinged periodontal relationship. Thus, this approach may represent an alternative means for periodontal alveolar bone graft in clinical settings.
由于涉及三种组织类型及其关系的复杂性,牙周附着装置的再生在临床上仍然具有挑战性。人重组骨形态发生蛋白-2(rhBMP-2)可加速骨和牙骨质的再生以及牙周韧带纤维的插入,但可能导致牙周关系紊乱、骨粘连和牙根吸收。本研究评估了一种使用复制缺陷型腺病毒工程化表达BMP-2基因的体外自体骨髓间充质干细胞(MSC)与普朗尼克F127(PF127)组合来再生牙周附着装置的新方法。在12只新西兰白兔身上手术制造了24个牙周缺损,并随机分为三个含MSC的实验组:腺病毒BMP-2组;腺病毒β半乳糖苷酶组;MSC组和一个对照组:仅PF127组。通过组织学评估再生的牙周附着装置,并从三维计算机断层扫描分析计算总再生骨体积。这种方法不仅再生了有沙比纤维插入的牙骨质,还再生了具有统计学意义的大量骨组织,重新建立了再生牙周附着装置各组成部分之间更正常的关系,这有利于维持牙周健康。使用干细胞作为载体的体外基因转移可能具有BMP-2释放较慢的优势,从而增加牙骨质生成。存在牙周附着装置的再生,而直接使用蛋白质(rhBMP-2)会产生紊乱的牙周关系。因此,这种方法可能代表了临床环境中牙周牙槽骨移植的一种替代手段。