The pH in the Microenvironment of Human Mesenchymal Stem Cells Is a Critical Factor for Optimal Osteogenesis in Tissue-Engineered Constructs
The pH in the Microenvironment of Human Mesenchymal Stem Cells Is a Critical Factor for Optimal Osteogenesis in Tissue-Engineered Constructs
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DOI：
10.1089/ten.tea.2013.0500
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发表时间：
2014-07-01
影响因子：
4.1
通讯作者：
Logeart-Avramoglou, Delphine
中科院分区：
文献类型：
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作者：
Monfoulet, Laurent-Emmanuel;Becquart, Pierre;Logeart-Avramoglou, Delphine
本研究旨在阐明组织工程（TE）构建体的细胞外微环境中局部pH值对与新组织形成相关的骨细胞功能的影响。为此，我们评估了与由人骨髓间充质干细胞（hBMSC）结合45 S5生物活性玻璃（BG）（一种诱导外部介质碱化的材料）制备的骨结构相关的成骨过程。含细胞BG构建体中测得的pH值约为8.0，即比测试的两种其他含细胞材料（羟基磷灰石/磷酸三钙[HA/TCP]和珊瑚）构建体中的pH值碱性高0.5U。当异位植入小鼠体内时，在含BG细胞的结构中没有新生骨组织，这与用HA/TCP或珊瑚陶瓷获得的结果相反，这始终促进异位骨的形成。此外，植入的HA/TCP：BG和珊瑚：BG结构的50：50复合材料显示pH值约为7.8，促进的骨组织量减少20-30倍。有趣的是，与在体外和体内测试的其他两种类型的材料构建体相比，BG构建体中的hBMSC活力不受影响。成骨分化（特别是碱性磷酸酶[ALP]活性和RUNX 2，ALP和BSP的基因表达）不受影响时，hBMSC维持在中等碱性pH值（7.54）pH值。最重要的是，存在一个pH范围（具体地，7.9-8.27），在该pH范围hBMSC增殖不受影响，但这些细胞的成骨分化被抑制。总而言之，这些发现提供了证据表明，TE结构微环境中的过度碱化（例如，由材料降解引起）对骨祖细胞的成骨分化产生不利影响。
The present study aimed at elucidating the effect of local pH in the extracellular microenvironment of tissueengineered (TE) constructs on bone cell functions pertinent to new tissue formation. To this aim, we evaluated the osteogenicity process associated with bone constructs prepared from human Bone marrow-derived mesenchymal stem cells (hBMSC) combined with 45S5 bioactive glass (BG), a material that induces alkalinization of the external medium. The pH measured in cell-containing BG constructs was around 8.0, that is, 0.5U more alkaline than that in two other cell-containing materials (hydroxyapatite/tricalcium phosphate [HA/TCP] and coral) constructs tested. When implanted ectopically in mice, there was no de novo bone tissue in the BG cell-containing constructs, in contrast to results obtained with either HA/TCP or coral ceramics, which consistently promoted the formation of ectopic bone. In addition, the implanted 50: 50 composites of both HA/TCP: BG and coral: BG constructs, which displayed a pH of around 7.8, promoted 20-30-fold less amount of bone tissue. Interestingly, hBMSC viability in BG constructs was not affected compared with the other two types of material constructs tested both in vitro and in vivo. Osteogenic differentiation (specifically, the alkaline phosphatase [ALP] activity and gene expression of RUNX2, ALP, and BSP) was not affected when hBMSC were maintained in moderate alkaline pH ( 7.54) pH values. Most importantly, there is a pH range (specifically, 7.9-8.27) at which hBMSC proliferation was not affected, but the osteogenic differentiation of these cells was inhibited. Altogether, these findings provided evidence that excessive alkalinization in the microenvironment of TE constructs (resulting, for example, from material degradation) affects adversely the osteogenic differentiation of osteoprogenitor cells.