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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Bone Marrow Mesenchymal Stem Cells Expressing Baculovirus-Engineered Bone Morphogenetic Protein-7 Enhance Rabbit Posterolateral Fusion
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Bone Marrow Mesenchymal Stem Cells Expressing Baculovirus-Engineered Bone Morphogenetic Protein-7 Enhance Rabbit Posterolateral Fusion

机译：表达杆状病毒工程骨形态发生蛋白7的骨髓间充质干细胞增强兔后外侧融合。

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Previous studies have suggested that bone marrow-derived mesenchymal stem cells (BMDMSCs) genetically modified with baculoviral bone morphogenetic protein-2 (Bac-BMP-2) vectors could achieve successful fusion in a femur defect model or in a spinal fusion model. In this study, BMDMSCs expressing BMP-7 (Bac-BMP-7-BMDMSCs) were generated. We hypothesized that Bac-BMP-7-BMDMSCs could secrete more BMP-7 than untransduced BMDMSCs in vitro and achieve spinal posterolateral fusion in a rabbit model. Eighteen rabbits underwent posterolateral fusion at L4-5. Group I (n = 6) was implanted with collagen-β-tricalcium phosphate (TCP)-hydroxyapatite (HA), Group II (n = 6) was implanted with collagen-β-TCP-HA plus BMDMSCs, and Group III (n = 6) was implanted with collagen-β-TCP-HA plus Bac-BMP-7-BMDMSCs. In vitro production of BMP-7 was quantified with an enzyme-linked immunosorbent assay (ELISA). Spinal fusion was examined using computed tomography (CT), manual palpation, and histological analysis. ELISA demonstrated that Bac-BMP-7-BMDMSCs produced four-fold to five-fold more BMP-7 than did BMDMSCs. In the CT results, 6 fused segments were observed in Group I (50%, 6/12), 8 in Group II (67%, 8/12), and 12 in Group III (100%, 12/12). The fusion rate, determined by manual palpation, was 0% (0/6) in Group I, 0% (0/6) in Group II, and 83% (5/6) in Group III. Histology showed that Group III had more new bone and matured marrow formation. In conclusion, BMDMSCs genetically transduced with the Bac-BMP-7 vector could express more BMP-7 than untransduced BMDMSCs. These Bac-BMP-7-BMDMSCs on collagen-β-TCP-HA scaffolds were able to induce successful spinal fusion in rabbits.
机译：先前的研究表明，用杆状病毒骨形态发生蛋白2（Bac-BMP-2）载体基因修饰的骨髓源间充质干细胞（BMDMSC）可以在股骨缺损模型或脊柱融合模型中成功融合。在这项研究中，生成了表达BMP-7的BMDMSC（Bac-BMP-7-BMDMSC）。我们假设Bac-BMP-7-BMDMSCs在体外可比未转导的BMDMSCs分泌更多的BMP-7，并在兔模型中实现脊柱后外侧融合。在L4-5对18只兔子进行后外侧融合。第一组（n = 6）植入胶原蛋白-β-磷酸三钙（TCP）-羟基磷灰石（HA），第二组（n = 6）植入胶原蛋白-β-TCP-HA+ BMDMSCs，第三组（n = 6）植入胶原蛋白-β-TCP-HA加Bac-BMP-7-BMDMSC。 BMP-7的体外产生通过酶联免疫吸附测定（ELISA）进行定量。使用计算机断层扫描（CT），手动触诊和组织学分析检查脊柱融合。 ELISA显示，Bac-BMP-7-BMDMSC产生的BMP-7比BMDMSC多四到五倍。在CT结果中，I组观察到6个融合节段（50％，6/12），II组观察到8个融合节段（67％，8/12），III组观察到12个融合节段（100％，12/12）。通过手动触诊确定的融合率，第一组为0％（0/6），第二组为0％（0/6），第三组为83％（5/6）。组织学显示，第三组具有更多的新骨和成熟的骨髓形成。总之，用Bac-BMP-7载体基因转导的BMDMSC可以比未转导的BMDMSC表达更多的BMP-7。这些在胶原蛋白-β-TCP-HA支架上的Bac-BMP-7-BMDMSC能够诱导兔成功的脊柱融合。

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