Dosage and composition of bioactive glasses differentially regulate angiogenic and osteogenic response of human MSCs.
Dosage and composition of bioactive glasses differentially regulate angiogenic and osteogenic response of human MSCs.
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DOI：
10.1002/jbm.a.36470
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发表时间：
2018-10
期刊：
影响因子：
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通讯作者：
T. Qazi;J. Berkmann;J. Schoon;S. Geissler;G. Duda;A. Boccaccini;E. Lippens
中科院分区：
文献类型：
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作者：
T. Qazi;J. Berkmann;J. Schoon;S. Geissler;G. Duda;A. Boccaccini;E. Lippens
骨折部位的血管化和细胞介导的矿化基质沉积是损伤后骨再生成功的关键因素。陶瓷生物材料如生物活性玻璃（BAGs）释放生物活性离子，在骨缺损再生中显示出良好的效果。然而，目前尚不清楚生物活性离子的剂量和组成如何影响人间充质基质细胞（MSCs）的血管生成和成骨行为。在这里，我们发现暴露于1393和45S5 bag的离子溶解产物可以以剂量和成分依赖的方式引起原代MSCs的不同血管生成和成骨反应。在条件培养基（CM）中，暴露于45S5的MSCs中检测到较高浓度的促血管生成因子VEGF、HGF、PIGF、血管生成素和血管生成素，但1393，BAGs中没有检测到。将这种CM应用于人脐静脉内皮细胞（HUVECs），在体外形成了强健的二维管。通过基因表达分析和矿化分析评估MSCs的成骨分化。与其他各组相比，低浓度（0.1% w/v） 1393 bag显著提高了RUNX2和ALP基因的表达，诱导基质矿化的发生时间提前。我们进一步测试了同时暴露于这两种袋子是否会促进MSCs的血管生成分泌和成骨分化，但没有发现支持这一假设的证据。我们的研究结果提供了BAG成分依赖的人间充质干细胞再生功能增强的证据，同时也强调了将基于BAG的方法转化为安全有效的临床治疗方法的剂量-反应关系的体外评估的重要性。©2018 Wiley期刊公司中国生物医学工程学报，2016,31(1):557 - 557。, 2018年。
Vascularization of the fracture site and cell-mediated deposition of the mineralized matrix are crucial determinants for successful bone regeneration after injury. Ceramic biomaterials such as bioactive glasses (BAGs) that release bioactive ions have shown promising results in bone defect regeneration. However, it remains unclear how the dosage and composition of bioactive ions influence the angiogenic and osteogenic behavior of primary human mesenchymal stromal cells (MSCs). Here, we show that exposure to ionic dissolution products from 1393 and 45S5 BAGs can evoke distinct angiogenic and osteogenic responses from primary MSCs in a dose- and composition-dependent manner. Significantly higher concentrations of the pro-angiogenic factors VEGF, HGF, PIGF, angiopoietin, and angiogenin were detected in conditioned media (CM) from MSCs exposed to 45S5, but not 1393, BAGs. Application of this CM to human umbilical vein endothelial cells (HUVECs) resulted in robust 2D tube formation in vitro. Osteogenic differentiation of MSCs was assessed by gene expression analysis and mineralization assays. Low concentrations (0.1% w/v) of 1393 BAGs significantly enhanced the gene expression of RUNX2 and ALP and induced an earlier onset of matrix mineralization compared to all other groups. We further tested whether simultaneous exposure to both BAGs would improve both angiogenic secretion and osteogenic differentiation of MSCs, and did not find evidence to support this hypothesis. Our results provide evidence of BAG composition-dependent enhancement of primary human MSCs' regenerative function, besides also underlining the importance of an in vitro evaluation of the dose-response relationship to translate BAG based approaches into safe and effective clinical therapies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2827-2837, 2018., 2018.