Endothelial cells stimulate osteogenic differentiation of mesenchymal stem cells on calcium phosphate scaffolds
Endothelial cells stimulate osteogenic differentiation of mesenchymal stem cells on calcium phosphate scaffolds
复制标题
DOI：
10.1002/term.1590
复制
发表时间：
2014-10-01
影响因子：
3.3
通讯作者：
Rychly, Joachim
中科院分区：
文献类型：
--
作者：
Bulnheim, Ulrike;Mueller, Petra;Rychly, Joachim
间充质干细胞（MSCs）与内皮细胞在体内的相互作用对于生物体的再生过程具有重要意义。为了设计基于这种相互作用的用于骨再生的组织工程的概念，研究了与人真皮微血管内皮细胞（HDMECs）共培养的人骨髓源性MSC的成骨分化。实验集中于在不同磷酸钙支架上与HDMEC共培养的MSC的调节。碱性磷酸酶（ALP）活性和各种成骨标志物的mRNA表达显着增加时，细胞与磷酸钙支架材料的组织培养聚苯乙烯相比，或单独培养时，骨髓间充质干细胞。此外，观察到骨桥蛋白和骨钙素的表达对细胞粘附的底物高度敏感。而这些晚期成骨标志物在聚苯乙烯上的共培养物中下调，它们在磷酸钙上上调，并且在测试的三种磷酸钙支架上差异表达。为了增强共培养中MSC的成骨分化，需要直接的细胞-细胞相互作用。关于两种细胞类型之间相互作用的分子机制，发现连接蛋白43在接触部位表达，更明显的是，内皮细胞在MSC上生长，这促进了由各种粘附受体介导的直接细胞相互作用。这项研究揭示了通过刺激MSC与内皮细胞的功能相互作用来设计适合骨再生的植入材料的重要发现。版权所有（C）2012约翰威利父子有限公司
The interaction of mesenchymal stem cells (MSCs) with endothelium in vivo is significant for regenerative processes in organisms. To design concepts for tissue engineering for bone regeneration based on this interaction, the osteogenic differentiation of human bone marrow-derived MSCs in a co-culture with human dermal microvascular endothelial cells (HDMECs) was studied. The experiments were focussed on the regulation of MSCs in a co-culture with HDMECs on different calcium phosphate scaffolds. Alkaline phosphatase (ALP) activity and mRNA expression of various osteogenic markers increased significantly when cells were co-cultured on materials with calcium phosphate scaffolds compared to tissue culture polystyrene or when MSCs were cultured alone. In addition, it was observed that the expression of osteopontin and osteocalcin was highly sensitive to the substrate for cell adhesion. Whereas these late osteogenic markers were down-regulated in co-cultures on polystyrene, they were up-regulated on calcium phosphate and moreover, were differentially expressed on the three calcium phosphate scaffolds tested. To enhance the osteogenic differentiation of MSCs in a co-culture, direct cell-cell interactions were required. Concerning molecular mechanisms in the interactions between both cell types, it was found that connexin 43 was expressed in contact sites and more apparently, endothelial cells grew over the MSCs, which facilitated direct cellular interactions mediated by various adhesion receptors. This study revealed significant findings for the design of implant materials suitable for regeneration of bone by stimulating the functional interaction of MSCs with endothelial cells. Copyright (C) 2012 John Wiley & Sons, Ltd.