Nakajima K, Abe T, Tanaka M, Hara Y
Department of Periodontology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
J Periodontal Res. 2008 Dec;43(6):681-8. doi: 10.1111/j.1600-0765.2007.01072.x. Epub 2008 Jun 25.
In periodontal tissue engineering, the sourcing of most of the relevant cells is limited by poor accessibility, whereas the use of readily available gingival fibroblasts is hampered because of their inhibitory effects on bone formation. To address the latter drawback, we developed a new graft composed of fibronectin (FN) matrix-based multilayered cell sheets of human gingival fibroblasts modified to express alkaline phosphatase (ALP). This study was undertaken to investigate the effects of this graft, called the FN-ALP transplant, on the healing of periodontal defects in a rat model.
The FN-ALP transplants were grafted into periodontal fenestration bone defects in immunosuppressed rats. The process of periodontal healing was examined by histology, histomorphometry and immunohistochemistry. Grafted cells were tracked by immunostaining with human-specific antibodies. Control groups included non-transplanted empty defects and defects to which cell sheets without ALP induction had been grafted.
After implantation, the FN-ALP transplants healed alveolar bone defects by intramembranous ossification, with formation of cementum and periodontal ligament. Moreover, FN-ALP transplants increased new bone formation, by endochondral ossification, on the mandibular cortex adjacent to the defect. Grafted fibroblasts were located near host osteoblasts and chondrocyte precursor cells early in the ossification process but were undetectable on and in newly formed bone and cartilage.
These results indicate that the FN-ALP transplants support alveolar bone regeneration within the defect and augment bone formation outside the defect through the recruitment of host osteo/chondrogenic cells, suggesting their potential for periodontal tissue engineering applications.
在牙周组织工程中，大多数相关细胞的来源因获取困难而受限，而易于获得的牙龈成纤维细胞的使用则因它们对骨形成的抑制作用而受到阻碍。为了解决后一个缺点，我们开发了一种新的移植物，它由基于纤连蛋白（FN）基质的多层人牙龈成纤维细胞片组成，这些细胞片经过修饰以表达碱性磷酸酶（ALP）。本研究旨在探讨这种称为FN-ALP移植物的移植物对大鼠牙周缺损愈合的影响。
将FN-ALP移植物植入免疫抑制大鼠的牙周开窗性骨缺损中。通过组织学、组织形态计量学和免疫组织化学检查牙周愈合过程。用人类特异性抗体进行免疫染色追踪移植细胞。对照组包括未移植的空白缺损和移植了未诱导ALP的细胞片的缺损。
植入后，FN-ALP移植物通过膜内成骨愈合牙槽骨缺损，形成牙骨质和牙周韧带。此外，FN-ALP移植物通过软骨内成骨增加了缺损附近下颌骨皮质的新骨形成。在骨化过程早期，移植的成纤维细胞位于宿主成骨细胞和软骨细胞前体细胞附近，但在新形成的骨和软骨上及内部未检测到。
这些结果表明，FN-ALP移植物支持缺损内的牙槽骨再生，并通过募集宿主骨/软骨生成细胞增强缺损外的骨形成，表明它们在牙周组织工程应用中的潜力。
