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Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume

机译:骨形态发生蛋白2质粒DNA与趋化因子CXCL12的组合对骨形成的发作和体积产生累加效应

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Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.
机译:骨形态发生蛋白2(BMP-2)基因传递已显示出在基于细胞的组织工程体内诱导骨形成。此外,已知趋化性基质细胞衍生因子1α(SDF-1α,也称为CXCL12)会吸引多能基质细胞向其释放部位,在那里它可以增强血管形成并可能促进成骨分化。为了研究潜在的骨形成合作行为,我们研究了BMP-2和SDF-1α在小鼠异位骨形成中的联合释放。将具有BMP-2质粒DNA和/或SDF-1α负载在明胶微粒上的多能基质细胞播种和无细胞构建体皮下植入小鼠,历时6周。组织学分析和组织形态计量学表明,与接种细胞的构建体中的对照相比,BMP-2和SDF-1α的结合均增强了骨形成的开始和形成的骨体积。没有种子多能基质细胞的样品无法诱导任何骨形成。我们得出的结论是,向基于细胞的藻酸盐的骨形态发生蛋白2质粒DNA构建体中添加基质细胞衍生因子1α对骨形成具有累加作用,可以认为是骨再生的有前途的组合。

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