Endo Masaki, Kuroda Shinji, Kondo Hisatomo, Maruoka Yutaka, Ohya Keiichi, Kasugai Shohei
Oral Implantology and Regenerative Dental Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Tissue Eng. 2006 Mar;12(3):489-97. doi: 10.1089/ten.2006.12.489.
Gene-activated matrix (GAM) is a matrix, such as collagen-containing plasmid vector, that encodes a protein to stimulate tissue regeneration. In the original GAM system, gene transfer efficiency was extremely low. We have recently reported that modifying GAM with calcium-phosphate precipitates (CaP) enhances the efficiency of gene transfer. The purpose of this study was to evaluate the effects of our modified GAM on tissue regeneration. We prepared critical size segmental bone defects in rat tibiae and transplanted GAM consisting of bovine atelocollagen and expression plasmid vector (bmp2), which encodes human BMP2, with or without CaP. The tibiae were later examined radiographically, histologically, and mechanically. Implantation of bmp2-CaP-collagen at 12 microg bmp2 bridged the bone defect at 4 weeks, and the strength of the bone was comparable to that of an intact tibia at 6 weeks. Implantation of bmp2-collagen at the same dose of bmp2 bridged the defect to a smaller extent. Neither collagen alone nor vacant vector-CaP-collagen bridged the defect. These results indicate that our modified GAM with CaP has the potential to be effective in tissue regeneration at lower plasmid DNA doses than used in previous studies.
基因激活基质（GAM）是一种基质，例如含胶原蛋白的质粒载体，其编码一种刺激组织再生的蛋白质。在最初的GAM系统中，基因转移效率极低。我们最近报道，用磷酸钙沉淀（CaP）修饰GAM可提高基因转移效率。本研究的目的是评估我们改良的GAM对组织再生的影响。我们在大鼠胫骨中制备了临界尺寸的节段性骨缺损，并移植了由牛去端胶原蛋白和表达质粒载体（bmp2，其编码人BMP2）组成的GAM，添加或不添加CaP。随后对胫骨进行影像学、组织学和力学检查。植入含12微克bmp2的bmp2-CaP-胶原蛋白在4周时桥接了骨缺损，并且在6周时骨强度与完整胫骨相当。植入相同剂量bmp2的bmp2-胶原蛋白在较小程度上桥接了缺损。单独的胶原蛋白或空载体-CaP-胶原蛋白均未桥接缺损。这些结果表明，我们改良的含CaP的GAM有潜力在比先前研究中使用的更低质粒DNA剂量下有效促进组织再生。
