New England Musculoskeletal Institute, Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030-5456, USA.
Mol Ther. 2011 May;19(5):960-8. doi: 10.1038/mt.2011.2. Epub 2011 Feb 22.
Ex-vivo regional gene therapy with bone marrow cells (BMCs) overexpressing bone morphogenetic protein-2 (BMP-2) has demonstrated efficacy in healing critical sized bone defects in preclinical studies. The purpose of this preclinical study was to compare the osteoinductive potential of a novel "same day" ex-vivo regional gene therapy versus a traditional two-step approach, which involves culture expansion of the donor cells before implantation. In the "same day" strategy buffy coat cells were harvested from the rat bone marrow, transduced with a lentiviral vector-expressing BMP-2 for 1 hour and implanted into a rat femoral defect in the same sitting. There was no significant difference (P = 0.22) with respect to the radiographic healing rates between the femoral defects treated with the "same day" strategy (13/13; 100%) versus the traditional two-step approach (11/14; 78%). However, the femoral defects treated with the "same day" strategy induced earlier radiographic bone healing (P = 0.004) and higher bone volume (BV) [micro-computed tomography (micro-CT); P < 0.001]. The "same day" strategy represents a significant advance in the field of ex-vivo regional gene therapy because it offers a solution to limitations associated with the culture expansion process required in the traditional ex vivo approach. This strategy should be cost-effective when adapted for human use.
体外局部骨髓细胞（BMCs）过表达骨形成蛋白-2（BMP-2）的基因治疗在临床前研究中已证明能有效治疗临界尺寸的骨缺损。本临床前研究的目的是比较新型“当日”体外局部基因治疗与传统两步法的成骨潜力，后者涉及供体细胞植入前的培养扩增。在“当日”策略中，从大鼠骨髓中采集白细胞层，用表达 BMP-2 的慢病毒载体转导 1 小时，然后在同一部位植入大鼠股骨缺损部位。在接受“当日”策略治疗的股骨缺损（13/13；100%）与传统两步法治疗的股骨缺损（11/14；78%）之间，放射学愈合率没有显著差异（P=0.22）。然而，“当日”策略治疗的股骨缺损更早地诱导放射学骨愈合（P=0.004），并具有更高的骨体积（BV）[微计算机断层扫描（micro-CT）；P<0.001]。“当日”策略是体外局部基因治疗领域的重大进展，因为它提供了一种解决方案，可以克服传统体外方法中与培养扩增过程相关的限制。当适应于人类使用时，这种策略应该具有成本效益。
