An injectable method for noninvasive spine fusion.
An injectable method for noninvasive spine fusion.
复制标题
DOI：
10.1016/j.spinee.2010.12.011
复制
发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Olmsted-Davis EA
中科院分区：
文献类型：
--
作者：
Olabisi RM;Lazard Z;Heggeness MH;Moran KM;Hipp JA;Dewan AK;Davis AR;West JL;Olmsted-Davis EA
骨形态发生蛋白（BMP）诱导骨形成，但难以定位，随后从感兴趣的部位扩散和短半衰期降低了蛋白质的功效。目前，脊柱融合需要剥离，去皮质的横突，和自体移植收获程序。即使与BMP结合，临床脊柱融合术也有很高的失败率，可能是因为难以定位足够水平的BMP。目标是通过单次注射基于细胞的基因治疗系统实现可靠的脊柱融合，而无需任何手术干预。将87只免疫缺陷（n=44）和免疫活性（n=43）小鼠沿着棘旁肌肉组织注射，以快速诱导异位骨化（HO）并最终进行脊柱关节固定术。免疫缺陷和免疫活性小鼠注射成纤维细胞，转导腺病毒载体表达BMP 2，沿着棘旁肌肉组织。骨形成通过X线片、微计算机断层扫描和生物力学分析进行评价。早在2周时就获得了椎骨之间的新桥接骨和与相邻骨骼骨的融合。早在注射基因治疗系统后2周，脊柱屈曲-伸展也发生减少，所有动物在4周时融合率均超过90%，无论其遗传背景如何。将我们的基于细胞的系统注射到棘旁肌肉组织中诱导脊柱融合，这既不依赖于细胞类型也不依赖于免疫状态。这些研究是第一个利用HO在免疫能力模型作为临床相关脊柱融合的非侵入性注射系统，并可能有一天影响人类脊柱关节融合术。
Bone morphogenetic proteins (BMPs) induce bone formation but are difficult to localize, and subsequent diffusion from the site of interest and short half-life reduce the efficacy of the protein. Currently, spine fusion requires stripping, decortications of the transverse processes, and an autograft harvest procedure. Even in combination with BMPs, clinical spinal fusion has a high failure rate, presumably because of difficulties in localizing sufficient levels of BMP. The goal was to achieve reliable spine fusion through a single injection of a cell-based gene therapy system without the need for any surgical intervention. Eighty-seven immunodeficient (n=44) and immune-competent (n=43) mice were injected along the paraspinous musculature to achieve rapid induction of heterotopic ossification (HO) and ultimately spinal arthrodesis. Immunodeficient and immune-competent mice were injected with fibroblasts, transduced with an adenoviral vector to express BMP2, along the paraspinous musculature. Bone formation was evaluated via radiographs, microcomputed tomography, and biomechanical analysis. ew bridging bone between the vertebrae and the fusion to adjacent skeletal bone was obtained as early as 2 weeks. Reduction in spine flexion-extension also occurred as early as 2 weeks after injection of the gene therapy system, with greater than 90% fusion by 4 weeks in all animals regardless of their genetic background. Injection of our cell-based system into the paraspinous musculature induces spinal fusion that is dependent neither on the cell type nor on the immune status. These studies are the first to harness HO in an immune-competent model as a noninvasive injectable system for clinically relevant spinal fusion and may one day impact human spinal arthrodesis.
登录
查看更多内容
影响因子：
4.2
作者：
Fouletier-Dilling, Christine M.;Gannon, Francis H.;Davis, Alan R.
通讯作者：
Davis, Alan R.
影响因子：
5.1
作者：
Gugala, Z;Olmsted-Davis, EA;Davis, AR
通讯作者：
Davis, AR
影响因子：
46.9
作者：
Lutolf, MR;Weber, FE;Hubbell, JA
通讯作者：
Hubbell, JA
影响因子：
30.8
作者：
Shore, EM;Xu, MQ;Kaplan, FS
通讯作者：
Kaplan, FS
影响因子：
20.3
作者：
Bollard, Catherine M.;Gottschalk, Stephen;Heslop, Helen E.
通讯作者：
Heslop, Helen E.