Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
Gene Ther. 2010 Jun;17(6):733-44. doi: 10.1038/gt.2010.13. Epub 2010 Mar 11.
Cell-mediated and direct adenoviral (Ad) vector gene therapies can induce bone regeneration, including dermal fibroblasts (DFbs). We compared two effective therapies, DFb-mediated and direct Ad vector delivery of bone morphogenetic protein-2 (BMP2), for relative efficacy in bone regeneration. Equine rib drill defects were treated by percutaneous injection of either DFb-BMP2 or an Ad-BMP2 vector. At week 6, both DFb-BMP2- and Ad-BMP2-treated rib defects had greater bone filling volume and mineral density, with DFb-BMP2 inducing greater bone volume and maturity in the cortical bone aspect of the defect than Ad-BMP2. The transplantation of DFb alone induced modest bone formation. Increased mineral density and bone turnover were evident in the cortical and cancellous bone directly adjacent to the healing drill defects treated with either DFb-BMP2 or Ad-BMP2. Using our cell/vector dosage and model, BMP2, whether delivered by the DFb vector or direct Ad vector, induced greater and robust bone regeneration. DFb-mediated BMP2 therapy promoted greater cortical bone regeneration than did direct gene delivery, possibly because of an increased cellularity of the bone healing site. BMP2 delivery, regardless of gene delivery method, increased the mineral density of the neighboring bone, which may be beneficial clinically in repairing or weak bone.
细胞介导和直接腺病毒（Ad）载体基因治疗可以诱导骨再生，包括皮肤成纤维细胞（DFbs）。我们比较了两种有效的治疗方法，DFb 介导的和直接 Ad 载体传递骨形态发生蛋白-2（BMP2），以评估其在骨再生中的相对疗效。通过皮内注射 DFb-BMP2 或 Ad-BMP2 载体来治疗马肋骨钻取缺陷。在第 6 周，DFb-BMP2 和 Ad-BMP2 治疗的肋骨缺陷都有更大的骨填充体积和矿密度，DFb-BMP2 比 Ad-BMP2 诱导更大的皮质骨骨量和成熟度。DFb 单独移植诱导适度的骨形成。在用 DFb-BMP2 或 Ad-BMP2 治疗的愈合钻取缺陷的皮质骨和松质骨直接相邻处，明显增加了矿密度和骨转换。使用我们的细胞/载体剂量和模型，BMP2 无论是通过 DFb 载体还是直接 Ad 载体传递，都能诱导更大和更强的骨再生。DFb 介导的 BMP2 治疗比直接基因传递能更好地促进皮质骨再生，可能是因为骨愈合部位的细胞增多。BMP2 传递，无论基因传递方法如何，都增加了邻近骨的矿密度，这在修复或弱骨方面可能具有临床益处。
