Engineered scaffolds based on mesenchymal stem cells/preosteoclasts extracellular matrix promote bone regeneration
Engineered scaffolds based on mesenchymal stem cells/preosteoclasts extracellular matrix promote bone regeneration
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基于间充质干细胞/前破骨细胞细胞外基质的工程支架促进骨再生
DOI：
10.1177/2041731420926918
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发表时间：
2020-06-01
影响因子：
8.2
通讯作者：
Dong, Shiwu
中科院分区：
文献类型：
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作者：
Dong, Rui;Bai, Yun;Dong, Shiwu
近年来，基于细胞外基质的组织工程骨是修复骨缺损的一种有前景的方法，其种子细胞大多是间充质干细胞。然而，骨重塑是一个复杂的生物过程，其中破骨细胞执行骨吸收，成骨细胞主导骨形成。这两种细胞的相互作用和耦合是骨修复的关键。因此，仅由间充质干细胞分泌的细胞外基质不能模拟复杂的骨再生微环境，而通过前破骨细胞添加细胞外基质可能有助于骨再生的有效策略。在这里，我们建立了基于间充质干细胞/前破骨细胞外基质的组织工程骨，并证明与单独的间充质干细胞相比，基于间充质干细胞/前破骨细胞外基质的工程支架显着增强了3毫米大鼠股骨缺损模型的成骨作用。基于间充质干细胞/破骨细胞前细胞外基质的组织工程骨释放的生物活性蛋白也促进间充质干细胞的体外迁移、粘附和成骨分化。对于其机制，进行iTRAQ标记的质谱分析，发现608个差异表达蛋白，包括IGFBP5和CXCL12。通过体外研究，我们证明主要由前破骨细胞释放的CXCL12和IGFBP5蛋白分别有助于间充质干细胞迁移和成骨分化。总体而言，我们的研究首次将前破骨细胞引入骨组织工程中，并优化利用不同细胞模拟天然骨再生环境构建基于细胞外基质的组织工程骨的策略，为骨组织工程提供了新的视野。
Recently, extracellular matrix-based tissue-engineered bone is a promising approach to repairing bone defects, and the seed cells are mostly mesenchymal stem cells. However, bone remodelling is a complex biological process, in which osteoclasts perform bone resorption and osteoblasts dominate bone formation. The interaction and coupling of these two kinds of cells is the key to bone repair. Therefore, the extracellular matrix secreted by the mesenchymal stem cells alone cannot mimic a complex bone regeneration microenvironment, and the addition of extracellular matrix by preosteoclasts may contribute as an effective strategy for bone regeneration. Here, we established the mesenchymal stem cell/preosteoclast extracellular matrix -based tissue-engineered bones and demonstrated that engineered-scaffolds based on mesenchymal stem cell/ preosteoclast extracellular matrix significantly enhanced osteogenesis in a 3 mm rat femur defect model compared with mesenchymal stem cell alone. The bioactive proteins released from the mesenchymal stem cell/ preosteoclast extracellular matrix based tissue-engineered bones also promoted the migration, adhesion, and osteogenic differentiation of mesenchymal stem cells in vitro. As for the mechanisms, the iTRAQ-labeled mass spectrometry was performed, and 608 differentially expressed proteins were found, including the IGFBP5 and CXCL12. Through in vitro studies, we proved that CXCL12 and IGFBP5 proteins, mainly released from the preosteoclasts, contributed to mesenchymal stem cells migration and osteogenic differentiation, respectively. Overall, our research, for the first time, introduce pre-osteoclast into the tissue engineering of bone and optimize the strategy of constructing extracellular matrix-based tissue-engineered bone using different cells to simulate the natural bone regeneration environment, which provides new sight for bone tissue engineering.