Department of Otolaryngology, School of Medicine, Catholic University of Sacred Heart, Rome, Italy.
Head Neck. 2010 Mar;32(3):310-8. doi: 10.1002/hed.21185.
Implantation of autologous skin fibroblasts transduced ex vivo with a replication-defective adenoviral vector, carrying the LIM mineralization protein-3 (Ad-LMP-3), and adsorbed on a hydroxyapatite/collagen (HA/COL) scaffold.
Twenty-seven Wistar rats were used. A 5- x 5-mm full-thickness defect was created in the exposed mandible. All animals were randomized into 3 experimental groups: (1) autologous dermal fibroblasts transduced with Ad-LMP-3 and adsorbed on the HA/COL; (2) nontransduced dermal fibroblasts adsorbed on the HA/COL scaffold; and (3) HA/COL scaffold without cells. Three-dimensional micro-CT (3DmicroCT or 3DmuCT) and histological analysis were performed.
Efficient neoosteogenesis was observed in animals treated with LMP-3-expressing cells (group 1) as soon as 4 weeks after surgery. Conversely, nonsignificant bone formation was detected in control animals (groups 2 and 3) at all time points tested.
These results suggest that the experimental approach based on transplantation of genetically modified autologous cells could provide an alternative treatment for cranio-maxillo-facial defects. Nonetheless, additional data from the study on larger bone defects must follow to foresee a clinical application in the near future.
将体外转导复制缺陷型腺病毒载体、携带 LIM 矿化蛋白-3（Ad-LMP-3）的自体皮肤成纤维细胞，吸附在羟磷灰石/胶原（HA/COL）支架上。
使用 27 只 Wistar 大鼠。在暴露的下颌骨上创建一个 5×5mm 的全层缺损。所有动物随机分为 3 个实验组：（1）转导 Ad-LMP-3 并吸附在 HA/COL 上的自体真皮成纤维细胞；（2）吸附在 HA/COL 支架上的未转导真皮成纤维细胞；（3）无细胞的 HA/COL 支架。进行三维微计算机断层扫描（3DmicroCT 或 3DmuCT）和组织学分析。
术后 4 周即可观察到表达 LMP-3 的细胞（第 1 组）治疗的动物中出现有效的新骨生成。相反，在所有测试时间点，对照组动物（第 2 组和第 3 组）均未检测到明显的骨形成。
这些结果表明，基于移植基因修饰的自体细胞的实验方法可为颅面缺损提供替代治疗。然而，必须进行更大骨缺损的研究以获得更多数据，以便在不久的将来预见临床应用。
