Skeletal Biotech Laboratory, Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem, Israel.
J Tissue Eng Regen Med. 2011 May;5(5):384-93. doi: 10.1002/term.324. Epub 2010 Aug 26.
Mechanical loading has been described as a highly important stimulus for improvements in the quality and strength of bone. It has also been shown that mechanical stimuli can induce the differentiation of mesenchymal stem cells (MSCs) along the osteogenic lineage. We have previously demonstrated the potent osteogenic effect of MSCs engineered to overexpress the BMP2 gene. In this study we investigated the effect of mechanical loading on BMP2-expressing MSC-like cells, using a special bioreactor designed to apply dynamic forces on cell-seeded hydrogels. Cell viability, alkaline phosphatase (ALP) activity, BMP2 secretion and mineralized substance formation in the hydrogels were quantified. We found that cell metabolism increased as high as 6.8-fold, ALP activity by 12.5-fold, BMP2 secretion by 182-fold and mineralized tissue formation by 1.72-fold in hydrogels containing MSC-like cells expressing BMP2, which were cultured in the presence of mechanical loading. We have shown that ex vivo mechanical loading had an additive effect on BMP2-induced osteogenesis in genetically engineered MSC-like cells. These data could be valuable for bone tissue-engineering strategies of the future.
机械加载已被描述为改善骨质量和强度的高度重要刺激因素。也已经表明，机械刺激可以诱导间充质干细胞（MSCs）沿着成骨谱系分化。我们之前已经证明了过表达 BMP2 基因的 MSC 工程细胞具有强大的成骨作用。在这项研究中，我们使用专门设计用于对细胞接种水凝胶施加动态力的生物反应器，研究了机械加载对表达 BMP2 的 MSC 样细胞的影响。定量测定了水凝胶中的细胞活力、碱性磷酸酶（ALP）活性、BMP2 分泌和矿化物质形成。我们发现，在含有表达 BMP2 的 MSC 样细胞的水凝胶中，当存在机械加载时，细胞代谢增加高达 6.8 倍，ALP 活性增加 12.5 倍，BMP2 分泌增加 182 倍，矿化组织形成增加 1.72 倍。我们已经表明，体外机械加载对基因工程 MSC 样细胞中 BMP2 诱导的成骨作用具有附加作用。这些数据对于未来的骨组织工程策略可能具有重要价值。
