Skeletal Biotech Laboratory, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Tissue Eng Part A. 2010 Dec;16(12):3679-86. doi: 10.1089/ten.TEA.2009.0786. Epub 2010 Sep 28.
Most spine fusion procedures involve the use of prosthetic fixation devices combined with autologous bone grafts rather than biological treatment. We had shown that spine fusion could be achieved by injection of bone morphogenetic protein-2 (BMP-2)-expressing mesenchymal stem cells (MSCs) into the paraspinal muscle. In this study, we hypothesized that posterior spinal fusion achieved using genetically modified MSCs would be mechanically comparable to that realized using a mechanical fixation. BMP-2-expressing MSCs were injected bilaterally into paravertebral muscles of the mouse lumbar spine. In one control group BMP-2 expression was inhibited. Microcomputed tomography and histological analyses were used to evaluate bone formation. For comparison, a group of mouse spines were bilaterally fused with stainless steel pins. The harvested spines were later tested using a custom four-point bending apparatus and structural bending stiffness was estimated. To assess the degree to which MSC vertebral fusion was targeted and to quantify the effects of fusion on adjacent spinal segments, images of the loaded spine curvature were analyzed to extract rigidity of the individual spinal segments. Bone bridging of the targeted vertebrae was observed in the BMP-2-expressing MSC group, whereas no bone formation was noted in any control group. The biomechanical tests showed that MSC-mediated spinal fusion was as effective as stainless steel pin-based fusion and significantly more rigid than the control groups. Local analysis showed that the distribution of stiffness in the MSC-based fusion group was similar to that in the steel pin fusion group, with the majority of spinal stiffness contributed by the targeted fusion at L3-L5. Our findings demonstrate that MSC-induced spinal fusion can convey biomechanical rigidity to a targeted segment that is comparable to that achieved using an instrumental fixation.
大多数脊柱融合手术都涉及使用假体固定装置和自体骨移植物，而不是生物治疗。我们已经证明，通过将表达骨形态发生蛋白-2（BMP-2）的间充质干细胞（MSCs）注射到椎旁肌肉中，可以实现脊柱融合。在这项研究中，我们假设使用基因修饰的 MSCs 进行的脊柱后路融合在机械性能上可与机械固定相媲美。将表达 BMP-2 的 MSCs 双侧注射到小鼠腰椎椎旁肌肉中。在一个对照组中，抑制了 BMP-2 的表达。使用微计算机断层扫描和组织学分析来评估骨形成。为了进行比较，一组小鼠脊柱用不锈钢钉双侧融合。收获的脊柱后来使用定制的四点弯曲装置进行测试，并估计结构弯曲刚度。为了评估 MSC 椎体融合的靶向程度，并量化融合对相邻脊柱节段的影响，对加载脊柱曲率的图像进行分析，以提取各个脊柱节段的刚度。在表达 BMP-2 的 MSC 组中观察到目标椎体的骨桥形成，而在任何对照组中均未观察到骨形成。生物力学测试表明，MSC 介导的脊柱融合与不锈钢钉基融合一样有效，并且比对照组更坚固。局部分析表明，基于 MSC 的融合组中的刚度分布与基于钢钉的融合组相似，大多数脊柱刚度由 L3-L5 处的靶向融合贡献。我们的研究结果表明，MSC 诱导的脊柱融合可以将生物力学刚度传递到目标节段，与使用仪器固定实现的刚度相当。
