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利用牙龈成纤维细胞进行骨形态发生蛋白-2 基因的体外传递可促进大鼠骨再生。

Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts promotes bone regeneration in rats.

机构信息

Department of Periodontology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.

出版信息

J Clin Periodontol. 2010 Mar;37(3):305-11. doi: 10.1111/j.1600-051X.2009.01522.x. Epub 2009 Dec 21.

Abstract

AIM

The aim of the present study was to investigate bone regeneration following ex vivo bone morphogenetic protein-2 (BMP-2) gene delivery using human gingival fibroblasts (HGFs) in rat calvarial defects.

MATERIALS AND METHODS

An 8 mm craniotomy defect was created in Sprague-Dawley rats. The animals were divided into four groups: (1) non-grafted group, the defect was left empty; (2) collagen matrix group, the defect was filled with collagen matrix only; (3) HGF group, the defect was filled with non-transduced HGFs on collagen matrix; (4) BMP-2/HGF group, the defect was filled with BMP-2 gene-transduced HGFs on collagen matrix. Animals were sacrificed at 2 and 4 weeks after surgery, and micro-computed tomographic and histologic observations were performed.

RESULTS

The BMP-2/HGF group showed promoted osseous healing of calvarial defects, as compared with the other groups. At both 2 and 4 weeks, regenerated bone area was significantly greater in the BMP-2/HGF group than the other three groups. Quite a few number of transplanted HGFs were observed within the regenerated bone tissues.

CONCLUSIONS

The results of this study suggest that ex vivo BMP-2 gene delivery induces prominent bone regeneration in vivo and HGFs may be useful as target cells for ex vivo gene therapy.

摘要

目的

本研究旨在探讨应用人牙龈成纤维细胞(HGFs)在大鼠颅骨缺损部位进行骨形态发生蛋白-2(BMP-2)基因转染后骨再生的情况。

材料与方法

在 Sprague-Dawley 大鼠颅骨上制作 8mm 的颅窗缺损。将动物分为四组:(1)未移植组,缺损处为空;(2)胶原基质组,仅用胶原基质填充缺损;(3)HGF 组,用非转导的 HGFs 在胶原基质上填充缺损;(4)BMP-2/HGF 组,用 BMP-2 基因转导的 HGFs 在胶原基质上填充缺损。手术后 2 周和 4 周处死动物,进行 micro-CT 和组织学观察。

结果

与其他组相比,BMP-2/HGF 组显示出促进颅骨缺损的骨愈合。在 2 周和 4 周时,BMP-2/HGF 组的再生骨面积明显大于其他三组。在再生骨组织中观察到相当数量的移植 HGFs。

结论

本研究结果表明,体外 BMP-2 基因转导可诱导体内显著的骨再生,HGFs 可能作为体外基因治疗的靶细胞。

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