Tensile Loading Modulates Bone Marrow Stromal Cell Differentiation and the Development of Engineered Fibrocartilage Constructs
Tensile Loading Modulates Bone Marrow Stromal Cell Differentiation and the Development of Engineered Fibrocartilage Constructs
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DOI：
10.1089/ten.tea.2009.0561
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发表时间：
2010-06-01
影响因子：
4.1
通讯作者：
Levenston, Marc E.
中科院分区：
文献类型：
--
作者：
Connelly, John T.;Vanderploeg, Eric J.;Levenston, Marc E.
骨髓基质细胞（BMSC）等间充质祖细胞是纤维软骨组织工程的有吸引力的细胞来源，但促进纤维软骨细胞特异性分化所需的信号类型或组合仍不清楚。本研究调查了循环拉伸载荷对 BMSC 软骨形成和工程纤维软骨发育的影响。使用定制加载系统将循环拉伸位移（10%，1 Hz）应用于 BMSC 接种的纤维蛋白构建体，短期（24 小时）或长期（1-2 周）。在软骨形成的早期阶段，24小时的循环张力刺激蛋白质和蛋白多糖的合成，但在后期阶段，张力仅增加蛋白质合成。间歇性循环张力一周显着增加了构建体中硫酸化糖胺聚糖和胶原蛋白的总含量，但这些差异在负载两周后消失。在延长的培养期间限制凝胶可防止纤维蛋白基质收缩，诱导胶原纤维排列，并增加硫酸化糖胺聚糖向培养基的释放。循环张力特异性刺激 I 型胶原蛋白 mRNA 表达和蛋白质合成，但对 II 型胶原蛋白、聚集蛋白聚糖或骨钙蛋白 mRNA 水平没有影响。总体而言，这些研究表明，软骨形成刺激和拉伸负荷的结合可促进骨髓间充质干细胞的纤维软骨细胞样分化，并有可能在体外指导纤维软骨的发育。
Mesenchymal progenitors such as bone marrow stromal cells (BMSCs) are an attractive cell source for fibrocartilage tissue engineering, but the types or combinations of signals required to promote fibrochondrocyte-specific differentiation remain unclear. The present study investigated the influences of cyclic tensile loading on the chondrogenesis of BMSCs and the development of engineered fibrocartilage. Cyclic tensile displacements (10%, 1 Hz) were applied to BMSC-seeded fibrin constructs for short (24 h) or extended (1-2 weeks) periods using a custom loading system. At early stages of chondrogenesis, 24 h of cyclic tension stimulated both protein and proteoglycan synthesis, but at later stages, tension increased protein synthesis only. One week of intermittent cyclic tension significantly increased the total sulfated glycosaminoglycan and collagen contents in the constructs, but these differences were lost after 2 weeks of loading. Constraining the gels during the extended culture periods prevented contraction of the fibrin matrix, induced collagen fiber alignment, and increased sulfated glycosaminoglycan release to the media. Cyclic tension specifically stimulated collagen I mRNA expression and protein synthesis, but had no effect on collagen II, aggrecan, or osteocalcin mRNA levels. Overall, these studies suggest that the combination of chondrogenic stimuli and tensile loading promotes fibrochondrocyte-like differentiation of BMSCs and has the potential to direct fibrocartilage development in vitro.