Combined Use of Mesenchymal Stromal Cell Sheet Transplantation and Local Injection of SDF-1 for Bone Repair in a Rat Nonunion Model
Combined Use of Mesenchymal Stromal Cell Sheet Transplantation and Local Injection of SDF-1 for Bone Repair in a Rat Nonunion Model
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联合使用间充质基质细胞片移植和局部注射 SDF-1 在大鼠骨不连模型中进行骨修复
DOI：
10.3727/096368916x690980
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Huang, Zhongming
中科院分区：
文献类型：
--
作者：
Chen, Guangnan;Fang, Tingting;Huang, Zhongming
骨不连的治疗在骨科是一个挑战。本研究探讨了使用间充质干细胞(MSC)片和局部注射基质细胞衍生因子-1(SDF-1)对骨形成的联合作用。在体外，我们发现SDF-1以剂量依赖的方式介导MSCs的迁移。SDF-1刺激对MSCs的增殖或成骨分化无直接影响。此外，结果表明，与培养的MSCs相比，MSC片中骨形态发生蛋白2、碱性磷酸酶、骨钙素和血管内皮生长因子的表达水平升高。通过X射线、微型计算机断层扫描(Micro-CT)、苏木精-伊红(H&E)染色、藏红-O染色和免疫组织化学方法评价骨折内的新骨形成。在大鼠骨折模型中，骨髓间充质干细胞移植到损伤部位并注射SDF-1后，在间隙内有明显的新骨形成。此外，在8周时，该组获得了完全的骨愈合。相比之下，对照组出现了骨不连。我们的研究提出了一种新的策略，包括使用MSC片结合局部注射SDF-1进行硬组织重建，如愈合骨不连和骨缺损。
Bone nonunion treatments pose a challenge in orthopedics. This study investigated the joint effects of using mesenchymal stem cell (MSC) sheets with local injection of stromal cell-derived factor-1 (SDF-1) on bone formation. In vitro, we found that migration of MSCs was mediated by SDF-1 in a dose-dependent manner. Moreover, stimulation with SDF-1 had no direct effect on the proliferation or osteogenic differentiation of MSCs. Furthermore, the results indicated elevated expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor in MSC sheets compared with MSCs cultured in medium. New bone formation in fractures was evaluated by X-ray, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, Safranin-O staining, and immunohistochemistry in vivo. In the rat bone fracture model, the MSC sheets transplanted into the injured site along with injection of SDF-1 showed significantly more new bone formation within the gap. Moreover, at 8 weeks, complete bone union was obtained in this group. In contrast, the control group showed nonunion of the bone. Our study suggests a new strategy involving the use of MSC sheets with a local injection of SDF-1 for hard tissue reconstruction, such as the healing of nonunions and bone defects.