Engineering of tooth-supporting structures by delivery of PDGF gene therapy vectors
Engineering of tooth-supporting structures by delivery of PDGF gene therapy vectors
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DOI：
10.1016/j.ymthe.2004.01.016
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发表时间：
2004-04-01
影响因子：
12.4
通讯作者：
Giannobile, WV
中科院分区：
文献类型：
--
作者：
Jin, QM;Anusaksathien, O;Giannobile, WV
血小板源性生长因子（PDGF）对伤口愈合包括牙齿支持结构的再生发挥有效作用。局部蛋白递送到牙周骨缺损的限制包括创伤部位的PDGF的瞬时生物活性和生物利用度。本研究的目的是确定体内PDGF-B基因转移的可行性，以刺激牙周组织再生在大的牙齿相关的牙槽骨缺损的大鼠。用单独的2.6%胶原基质或含有编码荧光素酶的腺病毒（对照）、PDGF-A（PDGF-1308）或PDGF-B的显性阴性突变体的基质处理牙周病病变（0.3 × 0.2 cm大小）。在基因递送后第3、7和14天收获组织块活检，并进行描述性组织学和组织形态计量学分析。用Ad-PDGF-B处理的缺损显示出更大的增殖细胞核抗原阳性染色细胞和强有力的证据表明骨和牙骨质再生超过了Ad-luciferase和Ad-PDGF-1308组。定量图像分析显示，与仅用Ad-荧光素酶或胶原基质治疗的病变相比，Ad-PDGF-B治疗部位的桥接骨增加近4倍，牙衬牙骨质修复增加6倍，这表明硬组织新生有限。此外，Xenogen In Vivo成像系统揭示了基因转移后21天内牙周病变处荧光素酶报告基因的持续和局部基因表达。这些结果表明，在体内直接基因转移PDGF-B刺激牙槽骨和牙骨质再生在大牙周缺损。利用PDGF-B的基因治疗可能为牙周组织工程的应用提供了潜力。
Platelet-derived growth factor (PDGF) exerts potent effects on wound healing including the regeneration of tooth-supporting structures. Limitations of topical protein delivery to periodontal osseous defects include transient biological activity and the bioavailability of PDGF at the wound site. The objective of this investigation was to determine the feasibility of in vivo PDGF-B gene transfer to stimulate periodontal tissue regeneration in large tooth-associated alveolar bone defects in rats. Periodontal lesions (0.3 x 0.2 cm in size) were treated with a 2.6% collagen matrix alone or a matrix containing adenoviruses encoding luciferase (control), a dominant negative mutant of PDGF-A (PDGF-1308), or PDGF-B. Block biopsies were harvested at 3, 7, and 14 days post-gene delivery and descriptive histology and histomorphometric analyses were performed. The defects treated with Ad-PDGF-B demonstrated greater proliferating cell nuclear antigen positively stained cells and strong evidence of bone and cementum regeneration beyond that of Ad-luciferase and Ad-PDGF-1308 groups. Quantitative image analysis showed a nearly fourfold increase in bridging bone and sixfold increase in tooth-lining cemental repair in the Ad-PDGF-B-treated sites compared to lesions treated with Ad-luciferase or collagen matrix alone, which showed limited hard tissue neogenesis. In addition, the Xenogen In Vivo Imaging System revealed sustained and localized gene expression of the luciferase reporter at the periodontal lesions for up to 21 days after gene transfer. These results indicate that in vivo direct gene transfer of PDGF-B stimulates alveolar bone and cementum regeneration in large periodontal defects. Gene therapy utilizing PDGF-B may offer the potential for periodontal tissue engineering applications.